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Occupational Cancers pp 319–342Cite as

Malignant Mesothelioma: Molecular Markers

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Abstract

Recent developments in the field of molecular biology have increased our understanding of the molecular features of malignant mesothelioma (MM). This knowledge, together with the development of sensitive and high throughput molecular techniques, has helped to identify biomarkers that not only facilitate early and differential diagnosis but also assist in the evaluation of the prognosis and effectiveness of the treatment provided. Similarly, these advances have also shed light on the etiology of the diseases, for example, exposures to different environmental factors. Importantly, the novel and more sensitive methods have made it possible to detect these biomarkers in body fluids like pleural effusions, plasma, serum, urine, and sputum, making them suitable for fast and early diagnosis, as well as for the follow-up of the disease without the need for tissue from the primary tumor for analysis.

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References

  1. Tiainen M, Tammilehto L, Mattson K, Knuutila S. Nonrandom chromosomal abnormalities in malignant pleural mesothelioma. Cancer Genet Cytogenet. 1988;33:251–74.

    Article  CAS  PubMed  Google Scholar 

  2. Hagemeijer A, Versnel MA, Van Drunen E, Moret M, Bouts MJ, van der Kwast TH, Hoogsteden HC. Cytogenetic analysis of malignant mesothelioma. Cancer Genet Cytogenet. 1990;47:1–28.

    Article  CAS  PubMed  Google Scholar 

  3. Chiosea S, Krasinskas A, Cagle PT, Mitchell KA, Zander DS, Dacic S. Diagnostic importance of 9p21 homozygous deletion in malignant mesotheliomas. Mod Pathol. 2008;21:742–7. https://doi.org/10.1038/modpathol.2008.45.

    Article  CAS  PubMed  Google Scholar 

  4. Factor RE, Dal Cin P, Fletcher JA, Cibas ES. Cytogenetics and fluorescence in situ hybridization as adjuncts to cytology in the diagnosis of malignant mesothelioma. Cancer. 2009;117:247–53.

    PubMed  Google Scholar 

  5. Kettunen E, Salmenkivi K, Vuopala K, Toljamo T, Kuosma E, Norppa H, Knuutila S, Kaleva S, Huuskonen MS, Anttila S. Copy number gains on 5p15, 6p11-q11, 7p12, and 8q24 are rare in sputum cells of individuals at high risk of lung cancer. Lung Cancer. 2006;54:169–76.

    Article  PubMed  Google Scholar 

  6. Björkqvist AM, Wolf M, Nordling S, Tammilehto L, Knuuttila A, Kere J, Mattson K, Knuutila S. Deletions at 14q in malignant mesothelioma detected by microsatellite marker analysis. Br J Cancer. 1999;81:1111–5.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Lindholm P, Salmenkivi K, Vauhkonen H, Nicholson A, Anttila S, Kinnula V, Knuutila S. Gene copy number analysis in malignant pleural mesothelioma using oligonucleotide array CGH. Cytogenet Genome Res. 2007;119:46–52. https://doi.org/10.1159/000109618.

    Article  CAS  PubMed  Google Scholar 

  8. Pylkkänen L, Sainio M, Ollikainen T, Mattson K, Nordling S, Carpén O, Linnainmaa K, Husgafvel-Pursiainen K. Concurrent LOH at multiple loci in human malignant mesothelioma with preferential loss of NF2 gene region. Oncol Rep. 2002;9:955–9.

    PubMed  Google Scholar 

  9. Tuononen K, Sarhadi VK, Wirtanen A, Rönty M, Salmenkivi K, Knuuttila A, Remes S, Telaranta-Keerie AI, Bloor S, Ellonen P, Knuutila S. Targeted resequencing reveals ALK fusions in non-small cell lung carcinomas detected by FISH, immunohistochemistry, and real-time RT-PCR: a comparison of four methods. Biomed Res Int. 2013;2013:757490. https://doi.org/10.1155/2013/757490.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Mitelman F, Johansson B, Mertens F. Mitelman database of chromosome aberrations and gene fusions in cancer. 2014. http://cgap.nci.nih.gov/Chromosomes/Mitelman.

  11. Nymark P, Kettunen E, Knuutila S. Tumors of the lung. In: Heim S, Mitelman F, editors. Cancer cytogenetics. Hoboken: Wiley; 2015.

    Google Scholar 

  12. Ribotta M, Roseo F, Salvio M, Castagneto B, Carbone M, Procopio A, Giordano A, Mutti L. Recurrent chromosome 6 abnormalities in malignant mesothelioma. Monaldi Arch Chest Dis. 1998;53:228–35.

    CAS  PubMed  Google Scholar 

  13. Björkqvist A-M, Tammilehto L, Nordling S, Nurminen M, Anttila S, Mattson K, Knuutila S. Comparison of DNA copy number changes in malignant mesothelioma, adenocarcinoma and large-cell anaplastic carcinoma of the lung. Br J Cancer. 1998;77:260–9.

    Article  PubMed  Google Scholar 

  14. Hylebos M, Van Camp G, Vandeweyer G, Fransen E, Beyens M, Cornelissen R, Suls A, Pauwels P, van Meerbeeck JP, Op de Beeck K. Large-scale copy number analysis reveals variations in genes not previously associated with malignant pleural mesothelioma. Oncotarget. 2017;8:113673–86. https://doi.org/10.18632/oncotarget.22817.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Kato S, Tomson BN, Buys TP, Elkin SK, Carter JL, Kurzrock R. Genomic landscape of malignant mesotheliomas. Mol Cancer Ther. 2016;15:2498–507. https://doi.org/10.1158/1535-7163.MCT-16-0229.

    Article  CAS  PubMed  Google Scholar 

  16. Borczuk AC, Pei J, Taub RN, Levy B, Nahum O, Chen J, Chen K, Testa JR. Genome-wide analysis of abdominal and pleural malignant mesothelioma with DNA arrays reveals both common and distinct regions of copy number alteration. Cancer Biol Ther. 2016;17:328–35. https://doi.org/10.1080/15384047.2016.1145850.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Chirac P, Maillet D, Lepretre F, Isaac S, Glehen O, Figeac M, Villeneuve L, Peron J, Gibson F, Galateau-Salle F, Gilly FN, Brevet M. Genomic copy number alterations in 33 malignant peritoneal mesothelioma analyzed by comparative genomic hybridization array. Hum Pathol. 2016;55:72–82. https://doi.org/10.1016/j.humpath.2016.04.015.

    Article  CAS  PubMed  Google Scholar 

  18. Krasinskas AM, Bartlett DL, Cieply K, Dacic S. CDKN2A and MTAP deletions in peritoneal mesotheliomas are correlated with loss of p16 protein expression and poor survival. Mod Pathol. 2010;23:531–8.

    Article  CAS  PubMed  Google Scholar 

  19. Pei J, Kruger WD, Testa JR. High-resolution analysis of 9p loss in human cancer cells using single nucleotide polymorphism-based mapping arrays. Cancer Genet Cytogenet. 2006;170:65–8.

    Article  CAS  PubMed  Google Scholar 

  20. Simon F, Johnen G, Krismann M, Muller K-M. Chromosomal alterations in early stages of malignant mesotheliomas. Virchows Arch. 2005;447:762–7.

    Article  PubMed  Google Scholar 

  21. Cheng JQ, Jhanwar SC, Klein WM, Bell DW, Lee W-C, Altomare DA, Nobori T, Olopade OI, Buckler AJ, Testa JR. p16 alterations and deletion mapping of 9p21-p22 in malignant mesothelioma. Cancer Res. 1994;54:5547–51.

    CAS  PubMed  Google Scholar 

  22. Illei PB, Rusch VW, Zakowski MF, Ladanyi M. Homozygous deletion of CDKN2A and codeletion of the methylthioadenosine phosphorylase gene in the majority of pleural mesotheliomas. Clin Cancer Res. 2003;9:2108–13.

    CAS  PubMed  Google Scholar 

  23. Prins JB, Williamson KA, Kamp MM, Van Hezik EJ, Van der Kwast TH, Hagemeijer A, Versnel MA. The gene for the cyclin-dependent-kinase-4 inhibitor, CDKN2A, is preferentially deleted in malignant mesothelioma. Int J Cancer. 1998;75:649–53.

    Article  CAS  PubMed  Google Scholar 

  24. Xio S, Li D, Vijg J, Sugarbaker DJ, Corson JM, Fletcher JA. Codeletion of p15 and p16 in primary malignant mesothelioma. Oncogene. 1995;11:511–5.

    CAS  PubMed  Google Scholar 

  25. Onofre FB, Onofre AS, Pomjanski N, Buckstegge B, Grote HJ, Bocking A. 9p21 deletion in the diagnosis of malignant mesothelioma in serous effusions additional to immunocytochemistry, DNA-ICM, and AgNOR analysis. Cancer. 2008;114:204–15. https://doi.org/10.1002/cncr.23413.

    Article  PubMed  Google Scholar 

  26. Dacic S, Kothmaier H, Land S, Shuai Y, Halbwedl I, Morbini P, Murer B, Comin C, Galateau-Salle F, Demirag F, Zeren H, Attanoos R, Gibbs A, Cagle P, Popper H. Prognostic significance of p16/cdkn2a loss in pleural malignant mesotheliomas. Virchows Arch. 2008;453:627–35. https://doi.org/10.1007/s00428-008-0689-3.

    Article  PubMed  Google Scholar 

  27. Reid A, de Klerk N, Ambrosini G, Olsen N, Pang SC, Musk AW. The additional risk of malignant mesothelioma in former workers and residents of Wittenoom with benign pleural disease or asbestosis. Occup Environ Med. 2005;62:665–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Ascoli V, Aalto Y, Carnovale-Scalzo C, Nardi F, Falzetti D, Mecucci C, Knuutila S. DNA copy number changes in familial malignant mesothelioma. Cancer Genet Cytogenet. 2001;127:80–2.

    Article  CAS  PubMed  Google Scholar 

  29. Musti M, Cavone D, Aalto Y, Scattone A, Serio G, Knuutila S. A cluster of familial malignant mesothelioma with del(9p) as the sole chromosomal anomaly. Cancer Genet Cytogenet. 2002;138:73–6.

    Article  CAS  PubMed  Google Scholar 

  30. Tammilehto L, Tuomi T, Tiainen M, Rautonen J, Knuutila S, Pyrhönen S, Mattson K. Malignant mesothelioma: clinical characteristics, asbestos mineralogy and chromosomal abnormalities of 41 patients. Eur J Cancer. 1992;28A:1373–9.

    Article  CAS  PubMed  Google Scholar 

  31. Jean D, Thomas E, Manie E, Renier A, de Reynies A, Lecomte C, Andujar P, Fleury-Feith J, Galateau-Salle F, Giovannini M, Zucman-Rossi J, Stern MH, Jaurand MC. Syntenic relationships between genomic profiles of fiber-induced murine and human malignant mesothelioma. Am J Pathol. 2011;178:881–94. https://doi.org/10.1016/j.ajpath.2010.10.039.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Krismann M, Müller K, Jaworska M, Johnen G. Molecular cytogenetic differences between histological subtypes of malignant mesotheliomas: DNA cytometry and comparative genomic hybridization of 90 cases. J Pathol. 2002;197:363–71.

    Article  CAS  PubMed  Google Scholar 

  33. Furukawa M, Toyooka S, Hayashi T, Yamamoto H, Fujimoto N, Soh J, Hashida S, Shien K, Asano H, Aoe K, Okabe K, Pass HI, Tsukuda K, Kishimoto T, Miyoshi S. DNA copy number gains in malignant pleural mesothelioma. Oncol Lett. 2015;10:3274–8. https://doi.org/10.3892/ol.2015.3652.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Yoshikawa Y, Emi M, Hashimoto-Tamaoki T, Ohmuraya M, Sato A, Tsujimura T, Hasegawa S, Nakano T, Nasu M, Pastorino S, Szymiczek A, Bononi A, Tanji M, Pagano I, Gaudino G, Napolitano A, Goparaju C, Pass HI, Yang H, Carbone M. High-density array-CGH with targeted NGS unmask multiple noncontiguous minute deletions on chromosome 3p21 in mesothelioma. Proc Natl Acad Sci U S A. 2016;113:13432–7. https://doi.org/10.1073/pnas.1612074113.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Bueno R, Stawiski EW, Goldstein LD, Durinck S, De Rienzo A, Modrusan Z, Gnad F, Nguyen TT, Jaiswal BS, Chirieac LR, Sciaranghella D, Dao N, Gustafson CE, Munir KJ, Hackney JA, Chaudhuri A, Gupta R, Guillory J, Toy K, Ha C, Chen YJ, Stinson J, Chaudhuri S, Zhang N, Wu TD, Sugarbaker DJ, de Sauvage FJ, Richards WG, Seshagiri S. Comprehensive genomic analysis of malignant pleural mesothelioma identifies recurrent mutations, gene fusions and splicing alterations. Nat Genet. 2016;48:407–16. https://doi.org/10.1038/ng.3520.

    Article  CAS  PubMed  Google Scholar 

  36. Tsao AS, Harun N, Fujimoto J, Devito V, Lee JJ, Kuhn E, Mehran R, Rice D, Moran C, Hong WK, Shen L, Suraokar M, Wistuba I. Elevated PDGFRB gene copy number gain is prognostic for improved survival outcomes in resected malignant pleural mesothelioma. Ann Diagn Pathol. 2014;18:140–5. https://doi.org/10.1016/j.anndiagpath.2014.02.005.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Hung YP, Dong F, Watkins JC, Nardi V, Bueno R, Dal Cin P, Godleski JJ, Crum CP, Chirieac LR. Identification of ALK rearrangements in malignant peritoneal mesothelioma. JAMA Oncol. 2018;4:235–8. https://doi.org/10.1001/jamaoncol.2017.2918.

    Article  PubMed  Google Scholar 

  38. Panagopoulos I, Thorsen J, Gorunova L, Micci F, Haugom L, Davidson B, Heim S. RNA sequencing identifies fusion of the EWSR1 and YY1 genes in mesothelioma with t(14,22)(q32;q12). Genes Chromosomes Cancer. 2013;52:733–40. https://doi.org/10.1002/gcc.22068

    Article  CAS  PubMed  Google Scholar 

  39. Murthy SS, Testa JR. Asbestos, chromosomal deletions, and tumor suppressor gene alterations in human malignant mesothelioma. J Cell Physiol. 1999;180:150–7.

    Article  CAS  PubMed  Google Scholar 

  40. Sekido Y. Genomic abnormalities and signal transduction dysregulation in malignant mesothelioma cells. Cancer Sci. 2010;101:1–6.

    Article  CAS  PubMed  Google Scholar 

  41. Carbone M, Yang H, Pass HI, Krausz T, Testa JR, Gaudino G. BAP1 and cancer. Nat Rev Cancer. 2013;13:153–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Cortese JF, Gowda AL, Wali A, Eliason JF, Pass HI, Everson RB. Common EGFR mutations conferring sensitivity to gefitinib in lung adenocarcinoma are not prevalent in human malignant mesothelioma. Int J Cancer. 2006;118:521–2.

    Article  CAS  PubMed  Google Scholar 

  43. Agatsuma N, Yasuda Y, Ozasa H. Malignant pleural mesothelioma harboring both G719C and S768I mutations of EGFR successfully treated with Afatinib. J Thorac Oncol. 2017;12:e141–3. https://doi.org/10.1016/j.jtho.2017.04.028.

    Article  PubMed  Google Scholar 

  44. Kang HC, Kim HK, Lee S, Mendez P, Kim JW, Woodard G, Yoon JH, Jen KY, Fang LT, Jones K, Jablons DM, Kim IJ. Whole exome and targeted deep sequencing identify genome-wide allelic loss and frequent SETDB1 mutations in malignant pleural mesotheliomas. Oncotarget. 2016;7:8321–31. https://doi.org/10.18632/oncotarget.7032

    PubMed  PubMed Central  Google Scholar 

  45. Mäki-Nevala S, Sarhadi VK, Knuuttila A, Scheinin I, Ellonen P, Lagström S, Rönty M, Kettunen E, Husgafvel-Pursiainen K, Wolff H, Knuutila S. Driver gene and novel mutations in asbestos-exposed lung adenocarcinoma and malignant mesothelioma detected by exome sequencing. Lung. 2016;194:125–35. https://doi.org/10.1007/s00408-015-9814-7.

    Article  CAS  PubMed  Google Scholar 

  46. Guo G, Chmielecki J, Goparaju C, Heguy A, Dolgalev I, Carbone M, Seepo S, Meyerson M, Pass HI. Whole-exome sequencing reveals frequent genetic alterations in BAP1, NF2, CDKN2A, and CUL1 in malignant pleural mesothelioma. Cancer Res. 2015;75:264–9. https://doi.org/10.1158/0008-5472.CAN-14-1008.

    Article  CAS  PubMed  Google Scholar 

  47. Ugurluer G, Chang K, Gamez ME, Arnett AL, Jayakrishnan R, Miller RC, Sio TT. Genome-based mutational analysis by next generation sequencing in patients with malignant pleural and peritoneal mesothelioma. Anticancer Res. 2016;36:2331–8.

    CAS  PubMed  Google Scholar 

  48. Alakus H, Yost SE, Woo B, French R, Lin GY, Jepsen K, Frazer KA, Lowy AM, Harismendy O. BAP1 mutation is a frequent somatic event in peritoneal malignant mesothelioma. J Transl Med. 2015;13:122. https://doi.org/10.1186/s12967-015-0485-1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Bueno R, De Rienzo A, Dong L, Gordon GJ, Hercus CF, Richards WG, Jensen RV, Anwar A, Maulik G, Chirieac LR, Ho KF, Taillon BE, Turcotte CL, Hercus RG, Gullans SR, Sugarbaker DJ. Second generation sequencing of the mesothelioma tumor genome. PLoS One. 2010;5:e10612.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. Dong L, Jensen RV, De Rienzo A, Gordon GJ, Xu Y, Sugarbaker DJ, Bueno R. Differentially expressed alternatively spliced genes in malignant pleural mesothelioma identified using massively parallel transcriptome sequencing. BMC Med Genet. 2009;10:149.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  51. Sugarbaker DJ, Richards WG, Gordon GJ, Dong L, De Rienzo A, Maulik G, Glickman JN, Chirieac LR, Hartman ML, Taillon BE, Du L, Bouffard P, Kingsmore SF, Miller NA, Farmer AD, Jensen RV, Gullans SR, Bueno R. Transcriptome sequencing of malignant pleural mesothelioma tumors. Proc Natl Acad Sci U S A. 2008;105:3521–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Lo Iacono M, Monica V, Righi L, Grosso F, Libener R, Vatrano S, Bironzo P, Novello S, Musmeci L, Volante M, Papotti M, Scagliotti GV. Targeted next-generation sequencing of cancer genes in advanced stage malignant pleural mesothelioma: a retrospective study. J Thorac Oncol. 2015;10:492–9. https://doi.org/10.1097/JTO.0000000000000436.

    Article  CAS  PubMed  Google Scholar 

  53. Hylebos M, Van Camp G, van Meerbeeck JP, Op de Beeck K. The genetic landscape of malignant pleural mesothelioma: results from massively parallel sequencing. J Thorac Oncol. 2016;11:1615–26. https://doi.org/10.1016/j.jtho.2016.05.020.

    Article  PubMed  Google Scholar 

  54. Guled M, Lahti L, Lindholm PM, Salmenkivi K, Bagwan I, Nicholson AG, Knuutila S. CDKN2A, NF2, and JUN are dysregulated among other genes by miRNAs in malignant mesothelioma—a miRNA microarray analysis. Genes Chromosomes Cancer. 2009;48:615–23.

    Article  CAS  PubMed  Google Scholar 

  55. Balatti V, Maniero S, Ferracin M, Veronese A, Negrini M, Ferrocci G, Martini F, Tognon MG. MicroRNAs dysregulation in human malignant pleural mesothelioma. J Thorac Oncol. 2011;6(5):844–51.

    Article  PubMed  Google Scholar 

  56. Benjamin H, Lebanony D, Rosenwald S, Cohen L, Gibori H, Barabash N, Ashkenazi K, Goren E, Meiri E, Morgenstern S, Perelman M, Barshack I, Goren Y, Edmonston TB, Chajut A, Aharonov R, Bentwich Z, Rosenfeld N, Cohen D. A diagnostic assay based on microRNA expression accurately identifies malignant pleural mesothelioma. J Mol Diagn. 2010;12:771–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Busacca S, Germano S, De Cecco L, Rinaldi M, Comoglio F, Favero F, Murer B, Mutti L, Pierotti M, Gaudino G. MicroRNA signature of malignant mesothelioma with potential diagnostic and prognostic implications. Am J Respir Cell Mol Biol. 2010;42:312–9.

    Article  CAS  PubMed  Google Scholar 

  58. Pass HI, Goparaju C, Ivanov S, Donington J, Carbone M, Hoshen M, Cohen D, Chajut A, Rosenwald S, Dan H, Benjamin S, Aharonov R. hsa-miR-29c∗ is linked to the prognosis of malignant pleural mesothelioma. Cancer Res. 2010;70:1916–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Ju L, Wu W, Yin X, Xiao Y, Jia Z, Lou J, Yu M, Ying S, Chen T, Jiang Z, Li W, Chen J, Zhang X, Zhu L. miR-30d is related to asbestos exposure and inhibits migration and invasion in NCI-H2452 cells. FEBS Open Bio. 2017;7:1469–79. https://doi.org/10.1002/2211-5463.12274.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Micolucci L, Akhtar MM, Olivieri F, Rippo MR, Procopio AD. Diagnostic value of microRNAs in asbestos exposure and malignant mesothelioma: systematic review and qualitative meta-analysis. Oncotarget. 2016;7:58606–37. https://doi.org/10.18632/oncotarget.9686

    Article  PubMed  PubMed Central  Google Scholar 

  61. Matsumoto S, Nabeshima K, Hamasaki M, Shibuta T, Umemura T. Upregulation of microRNA-31 associates with a poor prognosis of malignant pleural mesothelioma with sarcomatoid component. Med Oncol. 2014;31:303. https://doi.org/10.1007/s12032-014-0303-2.

    Article  CAS  PubMed  Google Scholar 

  62. Kirschner MB, Cheng YY, Armstrong NJ, Lin RC, Kao SC, Linton A, Klebe S, McCaughan BC, van Zandwijk N, Reid G. MiR-score: a novel 6-microRNA signature that predicts survival outcomes in patients with malignant pleural mesothelioma. Mol Oncol. 2015;9:715–26. https://doi.org/10.1016/j.molonc.2014.11.007.

    Article  CAS  PubMed  Google Scholar 

  63. De Santi C, Melaiu O, Bonotti A, Cascione L, Di Leva G, Foddis R, Cristaudo A, Lucchi M, Mora M, Truini A, Tironi A, Murer B, Boldorini R, Cipollini M, Gemignani F, Gasparini P, Mutti L, Landi S. Deregulation of miRNAs in malignant pleural mesothelioma is associated with prognosis and suggests an alteration of cell metabolism. Sci Rep. 2017;7:3140. https://doi.org/10.1038/s41598-017-02694-0.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Santarelli L, Strafella E, Staffolani S, Amati M, Emanuelli M, Sartini D, Pozzi V, Carbonari D, Bracci M, Pignotti E, Mazzanti P, Sabbatini A, Ranaldi R, Gasparini S, Neuzil J, Tomasetti M. Association of miR-126 with soluble mesothelin-related peptides, a marker for malignant mesothelioma. PLoS One. 2011;6:e18232.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Weber DG, Gawrych K, Casjens S, Brik A, Lehnert M, Taeger D, Pesch B, Kollmeier J, Bauer TT, Johnen G, Bruning T. Circulating miR-132-3p as a candidate diagnostic biomarker for malignant mesothelioma. Dis Markers. 2017;2017:9280170. https://doi.org/10.1155/2017/9280170.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Bononi I, Comar M, Puozzo A, Stendardo M, Boschetto P, Orecchia S, Libener R, Guaschino R, Pietrobon S, Ferracin M, Negrini M, Martini F, Bovenzi M, Tognon M. Circulating microRNAs found dysregulated in ex-exposed asbestos workers and pleural mesothelioma patients as potential new biomarkers. Oncotarget. 2016;7:82700–11. https://doi.org/10.18632/oncotarget.12408

    Article  PubMed  PubMed Central  Google Scholar 

  67. Cappellesso R, Galasso M, Nicole L, Dabrilli P, Volinia S, Fassina A. miR-130A as a diagnostic marker to differentiate malignant mesothelioma from lung adenocarcinoma in pleural effusion cytology. Cancer. 2017;125:635–43. https://doi.org/10.1002/cncy.21869.

    Article  CAS  Google Scholar 

  68. Cappellesso R, Nicole L, Caroccia B, Guzzardo V, Ventura L, Fassan M, Fassina A. Young investigator challenge: microRNA-21/MicroRNA-126 profiling as a novel tool for the diagnosis of malignant mesothelioma in pleural effusion cytology. Cancer Cytopathol. 2016;124:28–37. https://doi.org/10.1002/cncy.21646.

    Article  CAS  PubMed  Google Scholar 

  69. MacDiarmid JA, Brahmbhatt H. Minicells: versatile vectors for targeted drug or si/shRNA cancer therapy. Curr Opin Biotechnol. 2011;22:909–16. https://doi.org/10.1016/j.copbio.2011.04.008.

    Article  CAS  PubMed  Google Scholar 

  70. Andersen M, Grauslund M, Ravn J, Sorensen JB, Andersen CB, Santoni-Rugiu E. Diagnostic potential of miR-126, miR-143, miR-145, and miR-652 in malignant pleural mesothelioma. J Mol Diagn. 2014;16:418–30. https://doi.org/10.1016/j.jmoldx.2014.03.002.

    Article  CAS  PubMed  Google Scholar 

  71. Kirschner MB, Cheng YY, Badrian B, Kao SC, Creaney J, Edelman JJ, Armstrong NJ, Vallely MP, Musk AW, Robinson BW, McCaughan BC, Klebe S, Mutsaers SE, van Zandwijk N, Reid G. Increased circulating miR-625-3p: a potential biomarker for patients with malignant pleural mesothelioma. J Thorac Oncol. 2012;7:1184–91. https://doi.org/10.1097/JTO.0b013e3182572e83.

    Article  CAS  PubMed  Google Scholar 

  72. Weber DG, Johnen G, Bryk O, Jockel KH, Bruning T. Identification of miRNA-103 in the cellular fraction of human peripheral blood as a potential biomarker for malignant mesothelioma—a pilot study. PLoS One. 2012;7:e30221. https://doi.org/10.1371/journal.pone.0030221.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Birnie KA, Prele CM, Thompson PJ, Badrian B, Mutsaers SE. Targeting microRNA to improve diagnostic and therapeutic approaches for malignant mesothelioma. Oncotarget. 2017;8:78193–207. https://doi.org/10.18632/oncotarget.20409

    Article  PubMed  PubMed Central  Google Scholar 

  74. Wright CM, Kirschner MB, Cheng YY, O’Byrne KJ, Gray SG, Schelch K, Hoda MA, Klebe S, McCaughan B, van Zandwijk N, Reid G. Long non coding RNAs (lncRNAs) are dysregulated in malignant pleural mesothelioma (MPM). PLoS One. 2013;8:e70940. https://doi.org/10.1371/journal.pone.0070940.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Riquelme E, Suraokar MB, Rodriguez J, Mino B, Lin HY, Rice DC, Tsao A, Wistuba II. Frequent coamplification and cooperation between C-MYC and PVT1 oncogenes promote malignant pleural mesothelioma. J Thorac Oncol. 2014;9:998–1007. https://doi.org/10.1097/JTO.0000000000000202.

    Article  PubMed  PubMed Central  Google Scholar 

  76. Goto Y, Shinjo K, Kondo Y, Shen L, Toyota M, Suzuki H, Gao W, An B, Fujii M, Murakami H, Osada H, Taniguchi T, Usami N, Kondo M, Hasegawa Y, Shimokata K, Matsuo K, Hida T, Fujimoto N, Kishimoto T, Issa J-P, Sekido Y. Epigenetic profiles distinguish malignant pleural mesothelioma from lung adenocarcinoma. Cancer Res. 2009;69:9073–82.

    Article  CAS  PubMed  Google Scholar 

  77. Kemp CD, Rao M, Xi S, Inchauste S, Mani H, Fetsch P, Filie A, Zhang M, Hong JA, Walker RL, Zhu YJ, Ripley RT, Mathur A, Liu F, Yang M, Meltzer PA, Marquez VE, De Rienzo A, Bueno R, Schrump DS. Polycomb repressor complex-2 is a novel target for mesothelioma therapy. Clin Cancer Res. 2012;18:77–90. https://doi.org/10.1158/1078-0432.CCR-11-0962.

    Article  CAS  PubMed  Google Scholar 

  78. McLoughlin KC, Kaufman AS, Schrump DS. Targeting the epigenome in malignant pleural mesothelioma. Transl Lung Cancer Res. 2017;6:350–65. https://doi.org/10.21037/tlcr.2017.06.06

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Christensen BC, Marsit CJ, Houseman EA, Godleski JJ, Longacker JL, Zheng S, Yeh R-F, Wrensch MR, Wiemels JL, Karagas MR, Bueno R, Sugarbaker DJ, Nelson HH, Wiencke JK, Kelsey KT. Differentiation of lung adenocarcinoma, pleural mesothelioma, and nonmalignant pulmonary tissues using DNA methylation profiles. Cancer Res. 2009;69:6315–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Christensen BC, Houseman EA, Marsit CJ, Zheng S, Wrensch MR, Wiemels JL, Nelson HH, Karagas MR, Padbury JF, Bueno R, Sugarbaker DJ, Yeh RF, Wiencke JK, Kelsey KT. Aging and environmental exposures alter tissue-specific DNA methylation dependent upon CpG island context. PLoS Genet. 2009;5:e1000602.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  81. Tsou JA, Galler JS, Wali A, Ye W, Siegmund KD, Groshen S, Laird PW, Turla S, Koss MN, Pass HI, Laird-Offringa IA. DNA methylation profile of 28 potential marker loci in malignant mesothelioma. Lung Cancer. 2007;58:220–30.

    Article  PubMed  Google Scholar 

  82. Andersen M, Trapani D, Ravn J, Sorensen JB, Andersen CB, Grauslund M, Santoni-Rugiu E. Methylation-associated silencing of microRNA-126 and its host gene EGFL7 in malignant pleural mesothelioma. Anticancer Res. 2015;35:6223–9.

    CAS  PubMed  Google Scholar 

  83. Cheng YY, Kirschner MB, Cheng NC, Gattani S, Klebe S, Edelman JJ, Vallely MP, McCaughan BC, Jin HC, van Zandwijk N, Reid G. ZIC1 is silenced and has tumor suppressor function in malignant pleural mesothelioma. J Thorac Oncol. 2013;8:1317–28. https://doi.org/10.1097/JTO.0b013e3182a0840a.

    Article  CAS  PubMed  Google Scholar 

  84. Christensen B, Houseman E, Godleski J, Marsit C, Longacker J, Roelofs C, Karagas M, Wrensch M, Yeh R, Nelson H, Wiemels J, Zheng S, Wiencke J, Bueno R, Sugarbaker D, Kelsey K. Epigenetic profiles distinguish pleural mesothelioma from normal pleura and predict lung asbestos burden and clinical outcome. Cancer Res. 2009;69:227–34. https://doi.org/10.1158/0008-5472.CAN-08-2586.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Christensen B, Houseman E, Poage G, Godleski J, Bueno R, Sugarbaker D, Wiencke J, Nelson H, Marsit C, Kelsey K. Integrated profiling reveals a global correlation between epigenetic and genetic alterations in mesothelioma. Cancer Res. 2010;70:5686–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Christensen BC, Godleski JJ, Marsit CJ, Houseman EA, Lopez-Fagundo CY, Longacker JL, Bueno R, Sugarbaker DJ, Nelson HH, Kelsey KT. Asbestos exposure predicts cell cycle control gene promoter methylation in pleural mesothelioma. Carcinogenesis. 2008;29:1555–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Destro A, Ceresoli GL, Baryshnikova E, Garassino I, Zucali PA, De Vincenzo F, Bianchi P, Morenghi E, Testori A, Alloisio M, Santoro A, Roncalli M. Gene methylation in pleural mesothelioma: correlations with clinico-pathological features and patient’s follow-up. Lung Cancer. 2008;59:369–76.

    Article  PubMed  Google Scholar 

  88. Fischer JR, Ohnmacht U, Rieger N, Zemaitis M, Stoffregen C, Kostrzewa M, Buchholz E, Manegold C, Lahm H. Promoter methylation of RASSF1A, RARbeta and DAPK predict poor prognosis of patients with malignant mesothelioma. Lung Cancer. 2006;54:109–16.

    Article  PubMed  Google Scholar 

  89. Fujii M, Fujimoto N, Hiraki A, Gemba K, Aoe K, Umemura S, Katayama H, Takigawa N, Kiura K, Tanimoto M, Kishimoto T. Aberrant DNA methylation profile in pleural fluid for differential diagnosis of malignant pleural mesothelioma. Cancer Sci. 2012;103:510–4. https://doi.org/10.1111/j.1349-7006.2011.02180.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Kohno H, Amatya VJ, Takeshima Y, Kushitani K, Hattori N, Kohno N, Inai K. Aberrant promoter methylation of WIF-1 and SFRP1, 2, 4 genes in mesothelioma. Oncol Rep. 2010;24:423–31.

    CAS  PubMed  Google Scholar 

  91. Kubo T, Toyooka S, Tsukuda K, Sakaguchi M, Fukazawa T, Soh J, Asano H, Ueno T, Muraoka T, Yamamoto H, Nasu Y, Kishimoto T, Pass HI, Matsui H, Huh NH, Miyoshi S. Epigenetic silencing of microRNA-34b/c plays an important role in the pathogenesis of malignant pleural mesothelioma. Clin Cancer Res. 2011;17:4965–74. https://doi.org/10.1158/1078-0432.CCR-10-3040.

    Article  CAS  PubMed  Google Scholar 

  92. Muraoka T, Soh J, Toyooka S, Aoe K, Fujimoto N, Hashida S, Maki Y, Tanaka N, Shien K, Furukawa M, Yamamoto H, Asano H, Tsukuda K, Kishimoto T, Otsuki T, Miyoshi S. The degree of microRNA-34b/c methylation in serum-circulating DNA is associated with malignant pleural mesothelioma. Lung Cancer. 2013;82:485–90. https://doi.org/10.1016/j.lungcan.2013.09.017.

    Article  PubMed  Google Scholar 

  93. Nelson HH, Almquist LM, LaRocca JL, Plaza SL, Lambert-Messerlian GM, Sugarbaker DJ, Bueno R, Godleski JJ, Marsit CJ, Christensen BC, Kelsey KT. The relationship between tumor MSLN methylation and serum mesothelin (SMRP) in mesothelioma. Epigenetics. 2011;6:1029–34. https://doi.org/10.4161/epi.6.8.16074.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Tan K, Kajino K, Momose S, Masaoka A, Sasahara K, Shiomi K, Izumi H, Abe M, Ohtsuji N, Wang T, Hino O, Fujii H. Mesothelin (MSLN) promoter is hypomethylated in malignant mesothelioma, but its expression is not associated with methylation status of the promoter. Hum Pathol. 2010;41:1330–8. https://doi.org/10.1016/j.humpath.2010.03.002.

    Article  CAS  PubMed  Google Scholar 

  95. Toyooka S, Pass HI, Shivapurkar N, Fukuyama Y, Maruyama R, Toyooka KO, Gilcrease M, Farinas A, Minna JD, Gazdar AF. Aberrant methylation and simian virus 40 tag sequences in malignant mesothelioma. Cancer Res. 2001;61:5727–30.

    CAS  PubMed  Google Scholar 

  96. Tsou JA, Shen LY, Siegmund KD, Long TI, Laird PW, Seneviratne CK, Koss MN, Pass HI, Hagen JA, Laird-Offringa IA. Distinct DNA methylation profiles in malignant mesothelioma, lung adenocarcinoma, and non-tumor lung. Lung Cancer. 2005;47:193–204.

    Article  PubMed  Google Scholar 

  97. Wong L, Zhou J, Anderson D, Kratzke R. Inactivation of p16INK4a expression in malignant mesothelioma by methylation. Lung Cancer. 2002;38:131–6.

    Article  PubMed  Google Scholar 

  98. Cioce M, Ganci F, Canu V, Sacconi A, Mori F, Canino C, Korita E, Casini B, Alessandrini G, Cambria A, Carosi MA, Blandino R, Panebianco V, Facciolo F, Visca P, Volinia S, Muti P, Strano S, Croce CM, Pass HI, Blandino G. Protumorigenic effects of mir-145 loss in malignant pleural mesothelioma. Oncogene. 2014;33:5319–31. https://doi.org/10.1038/onc.2013.476.

    Article  CAS  PubMed  Google Scholar 

  99. Yu M, Zhang Y, Jiang Z, Chen J, Liu L, Lou J, Zhang X. Mesothelin (MSLN) methylation and soluble mesothelin-related protein levels in a Chinese asbestos-exposed population. Environ Health Prev Med. 2015;20:369–78. https://doi.org/10.1007/s12199-015-0477-z.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Gray SG, Fennell DA, Mutti L, O’Byrne KJ. In arrayed ranks: array technology in the study of mesothelioma. J Thorac Oncol. 2009;4:411–25.

    Article  PubMed  Google Scholar 

  101. Gueugnon F, Leclercq S, Blanquart C, Sagan C, Cellerin L, Padieu M, Perigaud C, Scherpereel A, Gregoire M. Identification of novel markers for the diagnosis of malignant pleural mesothelioma. Am J Pathol. 2011;178:1033–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Melaiu O, Cristaudo A, Melissari E, Di Russo M, Bonotti A, Bruno R, Foddis R, Gemignani F, Pellegrini S, Landi S. A review of transcriptome studies combined with data mining reveals novel potential markers of malignant pleural mesothelioma. Mutat Res. 2012;750:132–40. https://doi.org/10.1016/j.mrrev.2011.12.003.

    Article  CAS  PubMed  Google Scholar 

  103. Gordon G, Jensen R, Hsiao L, Gullans S, Blumenstock J, Ramaswamy S, Richards W, Sugarbaker D, Bueno R. Translation of microarray data into clinically relevant cancer diagnostic tests using gene expression ratios in lung cancer and mesothelioma. Cancer Res. 2002;62:4963–7.

    CAS  PubMed  Google Scholar 

  104. Holloway AJ, Diyagama DS, Opeskin K, Creaney J, Robinson BWS, Lake RA, Bowtell DDL. A molecular diagnostic test for distinguishing lung adenocarcinoma from malignant mesothelioma using cells collected from pleural effusions. Clin Cancer Res. 2006;12:5129–35.

    Article  CAS  PubMed  Google Scholar 

  105. Crispi S, Calogero RA, Santini M, Mellone P, Vincenzi B, Citro G, Vicidomini G, Fasano S, Meccariello R, Cobellis G, Menegozzo S, Pierantoni R, Facciolo F, Baldi A, Menegozzo M. Global gene expression profiling of human pleural mesotheliomas: identification of matrix metalloproteinase 14 (MMP-14) as potential tumour target. PLoS One. 2009;4:e7016.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  106. Gordon GJ, Dong L, Yeap BY, Richards WG, Glickman JN, Edenfield H, Mani M, Colquitt R, Maulik G, Van Oss B, Sugarbaker DJ, Bueno R. Four-gene expression ratio test for survival in patients undergoing surgery for mesothelioma. J Natl Cancer Inst. 2009;101:678–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Gordon GJ, Rockwell GN, Godfrey PA, Jensen RV, Glickman JN, Yeap BY, Richards WG, Sugarbaker DJ, Bueno R. Validation of genomics-based prognostic tests in malignant pleural mesothelioma. Clin Cancer Res. 2005;11:4406–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Lopez-Rios F, Chuai S, Flores R, Shimizu S, Ohno T, Wakahara K, Illei PB, Hussain S, Krug L, Zakowski MF, Rusch V, Olshen AB, Ladanyi M. Global gene expression profiling of pleural mesotheliomas: overexpression of Aurora kinases and P16/CDKN2A deletion as prognostic factors and critical evaluation of microarray-based prognostic prediction. Cancer Res. 2006;66:2970–9. https://doi.org/10.1158/0008-5472.CAN-05-3907.

    Article  CAS  PubMed  Google Scholar 

  109. Mohr S, Keith G, Galateau-Salle F, Icard P, Rihn B. Cell protection, resistance and invasiveness of two malignant mesotheliomas as assessed by 10K-microarray. Biochim Biophys Acta. 2004;1688:43–60.

    Article  CAS  PubMed  Google Scholar 

  110. Pass HI, Liu Z, Wali A, Bueno R, Land S, Lott D, Siddiq F, Lonardo F, Carbone M, Draghici S. Gene expression profiles predict survival and progression of pleural mesothelioma. Clin Cancer Res. 2004;10:849–59.

    Article  CAS  PubMed  Google Scholar 

  111. De Rienzo A, Yeap BY, Cibas ES, Richards WG, Dong L, Gill RR, Sugarbaker DJ, Bueno R. Gene expression ratio test distinguishes normal lung from lung tumors in solid tissue and FNA biopsies. J Mol Diagn. 2014;16:267–72. https://doi.org/10.1016/j.jmoldx.2013.11.008.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Wali A, Morin PJ, Hough CD, Lonardo F, Seya T, Carbone M, Pass HI. Identification of intelectin overexpression in malignant pleural mesothelioma by serial analysis of gene expression (SAGE). Lung Cancer. 2005;48:19–29.

    Article  PubMed  Google Scholar 

  113. Kuraoka M, Amatya VJ, Kushitani K, Mawas AS, Miyata Y, Okada M, Kishimoto T, Inai K, Nishisaka T, Sueda T, Takeshima Y. Identification of DAB2 and intelectin-1 as novel positive immunohistochemical markers of epithelioid mesothelioma by transcriptome microarray analysis for its differentiation from pulmonary adenocarcinoma. Am J Surg Pathol. 2017;41:1045–52. https://doi.org/10.1097/PAS.0000000000000852.

    Article  PubMed  Google Scholar 

  114. Hoang C, D’Cunha J, Kratzke M, Casmey C, Frizelle S, Maddaus M, Kratzke R. Gene expression profiling identifies matriptase overexpression in malignant mesothelioma. Chest. 2004;125:1843–52.

    Article  CAS  PubMed  Google Scholar 

  115. Kettunen E, Nicholson AG, Nagy B, Wikman H, Seppänen JK, Stjernvall T, Ollikainen T, Kinnula V, Nordling S, Hollmen J, Anttila S, Knuutila S. L1CAM, INP10, P-cadherin, tPA and ITGB4 over-expression in malignant pleural mesotheliomas revealed by combined use of cDNA and tissue microarray. Carcinogenesis. 2005;26:17–25.

    Article  CAS  PubMed  Google Scholar 

  116. Sun X, Wei L, Liden J, Hui G, Dahlman-Wright K, Hjerpe A, Dobra K. Molecular characterization of tumour heterogeneity and malignant mesothelioma cell differentiation by gene profiling. J Pathol. 2005;207:91–101.

    Article  CAS  PubMed  Google Scholar 

  117. Caldas J, Gehlenborg N, Kettunen E, Faisal A, Rönty M, Nicholson AG, Knuutila S, Brazma A, Kaski S. Data-driven information retrieval in heterogeneous collections of transcriptomics data links SIM2s to malignant pleural mesothelioma. Bioinformatics. 2011;28:246–53.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  118. Roe OD, Anderssen E, Sandeck H, Christensen T, Larsson E, Lundgren S. Malignant pleural mesothelioma: genome-wide expression patterns reflecting general resistance mechanisms and a proposal of novel targets. Lung Cancer. 2010;67:57–68.

    Article  PubMed  Google Scholar 

  119. Romagnoli S, Fasoli E, Vaira V, Falleni M, Pellegrini C, Catania A, Roncalli M, Marchetti A, Santambrogio L, Coggi G, Bosari S. Identification of potential therapeutic targets in malignant mesothelioma using cell-cycle gene expression analysis. Am J Pathol. 2009;174:762–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Borczuk A, Cappellini G, Kim H, Hesdorffer M, Taub R, Powell C. Molecular profiling of malignant peritoneal mesothelioma identifies the ubiquitin-proteasome pathway as a therapeutic target in poor prognosis tumors. Oncogene. 2007;26:610–7.

    Article  CAS  PubMed  Google Scholar 

  121. Ruosaari S, Hienonen-Kempas T, Puustinen A, Sarhadi V, Hollmen J, Knuutila S, Saharinen J, Wikman H, Anttila S. Pathways affected by asbestos exposure in normal and tumour tissue of lung cancer patients. BMC Med Genet. 2008;1:55.

    Google Scholar 

  122. Ordonez NG. Application of immunohistochemistry in the diagnosis of epithelioid mesothelioma: a review and update. Hum Pathol. 2013;44:1–19. https://doi.org/10.1016/j.humpath.2012.05.014.

    Article  CAS  PubMed  Google Scholar 

  123. Munson P, Shukla A. Exosomes: potential in cancer diagnosis and therapy. Medicines (Basel). 2015;2:310–27. https://doi.org/10.3390/medicines2040310.

    Article  CAS  Google Scholar 

  124. Cerciello F, Choi M, Nicastri A, Bausch-Fluck D, Ziegler A, Vitek O, Felley-Bosco E, Stahel R, Aebersold R, Wollscheid B. Identification of a seven glycopeptide signature for malignant pleural mesothelioma in human serum by selected reaction monitoring. Clin Proteomics. 2013;10:16. https://doi.org/10.1186/1559-0275-10-16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Creaney J, Dick IM, Leon JS, Robinson BW. A proteomic analysis of the malignant mesothelioma secretome using iTRAQ. Cancer Genomics Proteomics. 2017;14:103–17. https://doi.org/10.21873/cgp.20023

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Ziegler A, Cerciello F, Bigosch C, Bausch-Fluck D, Felley-Bosco E, Ossola R, Soltermann A, Stahel RA, Wollscheid B. Proteomic surfaceome analysis of mesothelioma. Lung Cancer. 2012;75:189–96. https://doi.org/10.1016/j.lungcan.2011.07.009.

    Article  PubMed  Google Scholar 

  127. Giusti L, Da Valle Y, Bonotti A, Donadio E, Ciregia F, Ventroni T, Foddis R, Giannaccini G, Guglielmi G, Cristaudo A, Lucacchini A. Comparative proteomic analysis of malignant pleural mesothelioma evidences an altered expression of nuclear lamin and filament-related proteins. Proteomics Clin Appl. 2014;8:258–68. https://doi.org/10.1002/prca.201300052.

    Article  CAS  PubMed  Google Scholar 

  128. Grosserueschkamp F, Bracht T, Diehl HC, Kuepper C, Ahrens M, Kallenbach-Thieltges A, Mosig A, Eisenacher M, Marcus K, Behrens T, Bruning T, Theegarten D, Sitek B, Gerwert K. Spatial and molecular resolution of diffuse malignant mesothelioma heterogeneity by integrating label-free FTIR imaging, laser capture microdissection and proteomics. Sci Rep. 2017;7:44829. https://doi.org/10.1038/srep44829.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Hegmans JP, Veltman JD, Fung ET, Verch T, Glover C, Zhang F, Allard WJ, T’Jampens D, Hoogsteden HC, Lambrecht BN, Aerts J. Protein profiling of pleural effusions to identify malignant pleural mesothelioma using SELDI-TOF MS. Technol Cancer Res Treat. 2009;8:323–32.

    Article  CAS  PubMed  Google Scholar 

  130. Kao SC, Kirschner MB, Cooper WA, Tran T, Burgers S, Wright C, Korse T, van den Broek D, Edelman J, Vallely M, McCaughan B, Pavlakis N, Clarke S, Molloy MP, van Zandwijk N, Reid G. A proteomics-based approach identifies secreted protein acidic and rich in cysteine as a prognostic biomarker in malignant pleural mesothelioma. Br J Cancer. 2016;114:524–31. https://doi.org/10.1038/bjc.2015.470.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Kuramitsu Y, Miyamoto H, Tanaka T, Zhang X, Fujimoto M, Ueda K, Tanaka T, Hamano K, Nakamura K. Proteomic differential display analysis identified upregulated astrocytic phosphoprotein PEA-15 in human malignant pleural mesothelioma cell lines. Proteomics. 2009;9:5078–89. https://doi.org/10.1002/pmic.200800284.

    Article  CAS  PubMed  Google Scholar 

  132. Mundt F, Johansson HJ, Forshed J, Arslan S, Metintas M, Dobra K, Lehtio J, Hjerpe A. Proteome screening of pleural effusions identifies galectin 1 as a diagnostic biomarker and highlights several prognostic biomarkers for malignant mesothelioma. Mol Cell Proteomics. 2014;13:701–15. https://doi.org/10.1074/mcp.M113.030775.

    Article  CAS  PubMed  Google Scholar 

  133. Ostroff RM, Mehan MR, Stewart A, Ayers D, Brody EN, Williams SA, Levin S, Black B, Harbut M, Carbone M, Goparaju C, Pass HI. Early detection of malignant pleural mesothelioma in asbestos-exposed individuals with a noninvasive proteomics-based surveillance tool. PLoS One. 2012;7:e46091. https://doi.org/10.1371/journal.pone.0046091.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Ou WB, Corson JM, Flynn DL, Lu WP, Wise SC, Bueno R, Sugarbaker DJ, Fletcher JA. AXL regulates mesothelioma proliferation and invasiveness. Oncogene. 2011;30:1643–52.

    Article  CAS  PubMed  Google Scholar 

  135. Galateau-Salle F, Churg A, Roggli V, Travis WD, World Health Organization Committee for Tumors of the P. The 2015 World Health Organization classification of tumors of the pleura: advances since the 2004 classification. J Thorac Oncol. 2016;11:142–54. https://doi.org/10.1016/j.jtho.2015.11.005.

    Article  PubMed  Google Scholar 

  136. He C, Wang B, Wan C, Yang T, Shen Y. Diagnostic value of D2-40 immunostaining for malignant mesothelioma: a meta-analysis. Oncotarget. 2017;8:64407–16. https://doi.org/10.18632/oncotarget.19041.

    Article  PubMed  PubMed Central  Google Scholar 

  137. Henzi T, Blum WV, Pfefferli M, Kawecki TJ, Salicio V, Schwaller B. SV40-induced expression of calretinin protects mesothelial cells from asbestos cytotoxicity and may be a key factor contributing to mesothelioma pathogenesis. Am J Pathol. 2009;174:2324–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Husain AN, Colby TV, Ordonez NG, Allen TC, Attanoos RL, Beasley MB, Butnor KJ, Chirieac LR, Churg AM, Dacic S, Galateau-Salle F, Gibbs A, Gown AM, Krausz T, Litzky LA, Marchevsky A, Nicholson AG, Roggli VL, Sharma AK, Travis WD, Walts AE, Wick MR. Guidelines for pathologic diagnosis of malignant mesothelioma: 2017 update of the consensus statement from the International Mesothelioma Interest Group. Arch Pathol Lab Med. 2018;142(1):89–108. https://doi.org/10.5858/arpa.2017-0124-RA.

    Article  CAS  PubMed  Google Scholar 

  139. Soini Y, Kinnula V, Kahlos K, Pääkkö P. Claudins in differential diagnosis between mesothelioma and metastatic adenocarcinoma of the pleura. J Clin Pathol. 2006;59:250–4. https://doi.org/10.1136/jcp.2005.028589.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Panou V, Vyberg M, Weinreich UM, Meristoudis C, Falkmer UG, Roe OD. The established and future biomarkers of malignant pleural mesothelioma. Cancer Treat Rev. 2015;41:486–95. https://doi.org/10.1016/j.ctrv.2015.05.001.

    Article  CAS  PubMed  Google Scholar 

  141. Travis WD. Sarcomatoid neoplasms of the lung and pleura. Arch Pathol Lab Med. 2010;134:1645–58. https://doi.org/10.1043/2010-0086-RAR.1.

    Article  PubMed  Google Scholar 

  142. Cedres S, Ponce-Aix S, Zugazagoitia J, Sansano I, Enguita A, Navarro-Mendivil A, Martinez-Marti A, Martinez P, Felip E. Analysis of expression of programmed cell death 1 ligand 1 (PD-L1) in malignant pleural mesothelioma (MPM). PLoS One. 2015;10:e0121071. https://doi.org/10.1371/journal.pone.0121071.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Combaz-Lair C, Galateau-Salle F, McLeer-Florin A, Le Stang N, David-Boudet L, Duruisseaux M, Ferretti GR, Brambilla E, Lebecque S, Lantuejoul S. Immune biomarkers PD-1/PD-L1 and TLR3 in malignant pleural mesotheliomas. Hum Pathol. 2016;52:9–18. https://doi.org/10.1016/j.humpath.2016.01.010.

    Article  CAS  PubMed  Google Scholar 

  144. Marchevsky AM, LeStang N, Hiroshima K, Pelosi G, Attanoos R, Churg A, Chirieac L, Dacic S, Husain A, Khoor A, Klebe S, Lantuejoul S, Roggli V, Vignaud JM, Weynard B, Sauter J, Henderson D, Nabeshima K, Galateau-Salle F. The differential diagnosis between pleural sarcomatoid mesothelioma and spindle cell/pleomorphic (sarcomatoid) carcinomas of the lung: evidence-based guidelines from the International Mesothelioma Panel and the MESOPATH National Reference Center. Hum Pathol. 2017;67:160–8. https://doi.org/10.1016/j.humpath.2017.07.015.

    Article  PubMed  Google Scholar 

  145. Klebe S, Mahar A, Henderson DW, Roggli VL. Malignant mesothelioma with heterologous elements: clinicopathological correlation of 27 cases and literature review. Mod Pathol. 2008;21:1084–94.

    Article  PubMed  Google Scholar 

  146. van der Bij S, Schaake E, Koffijberg H, Burgers JA, de Mol BA, Moons KG. Markers for the non-invasive diagnosis of mesothelioma: a systematic review. Br J Cancer. 2011;104:1325–33.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  147. Li D, Wang B, Long H, Wen F. Diagnostic accuracy of calretinin for malignant mesothelioma in serous effusions: a meta-analysis. Sci Rep. 2015;5:9507. https://doi.org/10.1038/srep09507.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Hollevoet K, Reitsma JB, Creaney J, Grigoriu BD, Robinson BW, Scherpereel A, Cristaudo A, Pass HI, Nackaerts K, Rodriguez Portal JA, Schneider J, Muley T, Di Serio F, Baas P, Tomasetti M, Rai AJ, van Meerbeeck JP. Serum mesothelin for diagnosing malignant pleural mesothelioma: an individual patient data meta-analysis. J Clin Oncol. 2012;30:1541–9. https://doi.org/10.1200/JCO.2011.39.6671.

    Article  PubMed  PubMed Central  Google Scholar 

  149. Melaiu O, Stebbing J, Lombardo Y, Bracci E, Uehara N, Bonotti A, Cristaudo A, Foddis R, Mutti L, Barale R, Gemignani F, Giamas G, Landi S. MSLN gene silencing has an anti-malignant effect on cell lines overexpressing mesothelin deriving from malignant pleural mesothelioma. PLoS One. 2014;9:e85935. https://doi.org/10.1371/journal.pone.0085935.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Yamaguchi N, Hattori K, Oh-eda M, Kojima T, Imai N, Ochi N. A novel cytokine exhibiting megakaryocyte potentiating activity from a human pancreatic tumor cell line HPC-Y5. J Biol Chem. 1994;269:805–8.

    CAS  PubMed  Google Scholar 

  151. Scholler N, Fu N, Yang Y, Ye Z, Goodman GE, Hellstrom KE, Hellstrom I. Soluble member(s) of the mesothelin/megakaryocyte potentiating factor family are detectable in sera from patients with ovarian carcinoma. Proc Natl Acad Sci U S A. 1999;96:11531–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Cui A, Jin XG, Zhai K, Tong ZH, Shi HZ. Diagnostic values of soluble mesothelin-related peptides for malignant pleural mesothelioma: updated meta-analysis. BMJ Open. 2014;4:e004145. https://doi.org/10.1136/bmjopen-2013-004145.

    Article  PubMed  PubMed Central  Google Scholar 

  153. Sapede C, Gauvrit A, Barbieux I, Padieu M, Cellerin L, Sagan C, Scherpereel A, Dabouis G, Gregoire M. Aberrant splicing and protease involvement in mesothelin release from epithelioid mesothelioma cells. Cancer Sci. 2008;99:590–4. https://doi.org/10.1111/j.1349-7006.2007.00715.x.

    Article  CAS  PubMed  Google Scholar 

  154. Beyer HL, Geschwindt RD, Glover CL, Tran L, Hellstrom I, Hellstrom KE, Miller MC, Verch T, Allard WJ, Pass HI, Sardesai NY. MESOMARK: a potential test for malignant pleural mesothelioma. Clin Chem. 2007;53:666–72. https://doi.org/10.1373/clinchem.2006.079327.

    Article  CAS  PubMed  Google Scholar 

  155. Creaney J, Robinson BWS. Malignant mesothelioma biomarkers: from discovery to use in clinical practice for diagnosis, monitoring, screening, and treatment. Chest. 2017;152:143–9. https://doi.org/10.1016/j.chest.2016.12.004.

    Article  PubMed  Google Scholar 

  156. Creaney J, Yeoman D, Musk AW, de Klerk N, Skates SJ, Robinson BW. Plasma versus serum levels of osteopontin and mesothelin in patients with malignant mesothelioma-which is best? Lung Cancer. 2011;74:55–60.

    Article  PubMed  Google Scholar 

  157. Clayton A, Mitchell JP, Court J, Mason MD, Tabi Z. Human tumor-derived exosomes selectively impair lymphocyte responses to interleukin-2. Cancer Res. 2007;67:7458–66. https://doi.org/10.1158/0008-5472.CAN-06-3456.

    Article  CAS  PubMed  Google Scholar 

  158. Greening DW, Ji H, Chen M, Robinson BW, Dick IM, Creaney J, Simpson RJ. Secreted primary human malignant mesothelioma exosome signature reflects oncogenic cargo. Sci Rep. 2016;6:32643. https://doi.org/10.1038/srep32643.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Arnold DT, De Fonseka D, Hamilton FW, Rahman NM, Maskell NA. Prognostication and monitoring of mesothelioma using biomarkers: a systematic review. Br J Cancer. 2017;116:731–41. https://doi.org/10.1038/bjc.2017.22.

    Article  PubMed  PubMed Central  Google Scholar 

  160. Weber DG, Casjens S, Johnen G, Bryk O, Raiko I, Pesch B, Kollmeier J, Bauer TT, Bruning T. Combination of MiR-103a-3p and mesothelin improves the biomarker performance of malignant mesothelioma diagnosis. PLoS One. 2014;9:e114483. https://doi.org/10.1371/journal.pone.0114483.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. Burt BM, Lee HS, Lenge De Rosen V, Hamaji M, Groth SS, Wheeler TM, Sugarbaker DJ. Soluble mesothelin-related peptides to monitor recurrence after resection of pleural mesothelioma. Ann Thorac Surg. 2017;104(5):1679–87. https://doi.org/10.1016/j.athoracsur.2017.06.042.

    Article  PubMed  Google Scholar 

  162. Tian L, Zeng R, Wang X, Shen C, Lai Y, Wang M, Che G. Prognostic significance of soluble mesothelin in malignant pleural mesothelioma: a meta-analysis. Oncotarget. 2017;8:46425–35. https://doi.org/10.18632/oncotarget.17436

    PubMed  PubMed Central  Google Scholar 

  163. Weber DG, Johnen G, Taeger D, Weber A, Gross IM, Pesch B, Kraus T, Bruning T, Gube M. Assessment of confounding factors affecting the tumor markers SMRP, CA125, and CYFRA21-1 in serum. Biomark Insights. 2010;5:1–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  164. De Santi C, Pucci P, Bonotti A, Melaiu O, Cipollini M, Silvestri R, Vymetalkova V, Barone E, Paolicchi E, Corrado A, Lepori I, Dell’Anno I, Pelle L, Vodicka P, Mutti L, Foddis R, Cristaudo A, Gemignani F, Landi S. Mesothelin promoter variants are associated with increased soluble mesothelin-related peptide levels in asbestos-exposed individuals. Occup Environ Med. 2017;74:456–63. https://doi.org/10.1136/oemed-2016-104024.

    Article  PubMed  Google Scholar 

  165. Boudville N, Paul R, Robinson BW, Creaney J. Mesothelin and kidney function-analysis of relationship and implications for mesothelioma screening. Lung Cancer. 2011;73:320–4.

    Article  PubMed  Google Scholar 

  166. Hollevoet K, Van Cleemput J, Thimpont J, De Vuyst P, Bosquee L, Nackaerts K, Germonpre P, Vansteelandt S, Kishi Y, Delanghe JR, van Meerbeeck JP. Serial measurements of mesothelioma serum biomarkers in asbestos-exposed individuals: a prospective longitudinal cohort study. J Thorac Oncol. 2011;6:889–95.

    Article  PubMed  Google Scholar 

  167. Creaney J, Olsen NJ, Brims F, Dick IM, Musk AW, de Klerk NH, Skates SJ, Robinson BW. Serum mesothelin for early detection of asbestos-induced cancer malignant mesothelioma. Cancer Epidemiol Biomark Prev. 2011;19:2238–46.

    Article  CAS  Google Scholar 

  168. Park EK, Sandrini A, Yates DH, Creaney J, Robinson BW, Thomas PS, Johnson AR. Soluble mesothelin-related protein in an asbestos-exposed population: the dust diseases board cohort study. Am J Respir Crit Care Med. 2008;178:832–7.

    Article  CAS  PubMed  Google Scholar 

  169. Pass HI, Lott D, Lonardo F, Harbut M, Liu Z, Tang N, Carbone M, Webb C, Wali A. Asbestos exposure, pleural mesothelioma, and serum osteopontin levels. N Engl J Med. 2005;353:1564–73.

    Article  CAS  PubMed  Google Scholar 

  170. Hu ZD, Liu XF, Liu XC, Ding CM, Hu CJ. Diagnostic accuracy of osteopontin for malignant pleural mesothelioma: a systematic review and meta-analysis. Clin Chim Acta. 2014;433:44–8. https://doi.org/10.1016/j.cca.2014.02.024.

    Article  CAS  PubMed  Google Scholar 

  171. Cristaudo A, Foddis R, Bonotti A, Simonini S, Vivaldi A, Guglielmi G, Ambrosino N, Canessa PA, Chella A, Lucchi M, Mussi A, Mutti L. Comparison between plasma and serum osteopontin levels: usefulness in diagnosis of epithelial malignant pleural mesothelioma. Int J Biol Markers. 2010;25:164–70.

    Article  CAS  PubMed  Google Scholar 

  172. Pass HI, Goparaju C, Espin-Garcia O, Donington J, Carbone M, Patel D, Chen Z, Feld R, Cho J, Gadgeel S, Wozniak A, Chachoua A, Leighl N, Tsao MS, de Perrot M, Xu W, Liu G. Plasma biomarker enrichment of clinical prognostic indices in malignant pleural mesothelioma. J Thorac Oncol. 2016;11:900–9. https://doi.org/10.1016/j.jtho.2016.02.006.

    Article  PubMed  PubMed Central  Google Scholar 

  173. Park EK, Thomas PS, Johnson AR, Yates DH. Osteopontin levels in an asbestos-exposed population. Clin Cancer Res. 2009;15:1362–6.

    Article  CAS  PubMed  Google Scholar 

  174. Constantinescu D, Vornicu M, Grigoriu C, Cozmei C, Grigoriu BD. Assaying for circulating osteopontin in practice: a technical note. Eur Respir J. 2010;35:1187–8.

    Article  CAS  PubMed  Google Scholar 

  175. Mastrangelo G, Marangi G, Ballarin MN, Michilin S, Fabricio AS, Valentini F, Lange JH, Fedeli U, Cegolon L, Gion M. Osteopontin, asbestos exposure and pleural plaques: a cross-sectional study. BMC Public Health. 2011;11:220.

    Article  PubMed  PubMed Central  Google Scholar 

  176. Shiomi K, Shiomi S, Ishinaga Y, Sakuraba M, Hagiwara Y, Miyashita K, Maeda M, Suzuki K, Takahashi K, Hino O. Impact of renal failure on the tumor markers of mesothelioma, N-ERC/mesothelin and osteopontin. Anticancer Res. 2011;31:1427–30.

    PubMed  Google Scholar 

  177. Napolitano A, Antoine DJ, Pellegrini L, Baumann F, Pagano I, Pastorino S, Goparaju CM, Prokrym K, Canino C, Pass HI, Carbone M, Yang H. HMGB1 and its hyperacetylated isoform are sensitive and specific serum biomarkers to detect asbestos exposure and to identify mesothelioma patients. Clin Cancer Res. 2016;22:3087–96. https://doi.org/10.1158/1078-0432.CCR-15-1130.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  178. Yang H, Rivera Z, Jube S, Nasu M, Bertino P, Goparaju C, Franzoso G, Lotze MT, Krausz T, Pass HI, Bianchi ME, Carbone M. Programmed necrosis induced by asbestos in human mesothelial cells causes high-mobility group box 1 protein release and resultant inflammation. Proc Natl Acad Sci U S A. 2010;107:12611–6. https://doi.org/10.1073/pnas.1006542107.

    Article  PubMed  PubMed Central  Google Scholar 

  179. Jube S, Rivera ZS, Bianchi ME, Powers A, Wang E, Pagano I, Pass HI, Gaudino G, Carbone M, Yang H. Cancer cell secretion of the DAMP protein HMGB1 supports progression in malignant mesothelioma. Cancer Res. 2012;72:3290–301. https://doi.org/10.1158/0008-5472.CAN-11-3481.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  180. Ying S, Jiang Z, He X, Yu M, Chen R, Chen J, Ru G, Chen Y, Chen W, Zhu L, Li T, Zhang Y, Guo X, Yin X, Zhang X, Lou J. Serum HMGB1 as a potential biomarker for patients with asbestos-related diseases. Dis Markers. 2017;2017:5756102. https://doi.org/10.1155/2017/5756102.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  181. Tabata C, Shibata E, Tabata R, Kanemura S, Mikami K, Nogi Y, Masachika E, Nishizaki T, Nakano T. Serum HMGB1 as a prognostic marker for malignant pleural mesothelioma. BMC Cancer. 2013;13:205. https://doi.org/10.1186/1471-2407-13-205.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  182. Pass HI, Levin SM, Harbut MR, Melamed J, Chiriboga L, Donington J, Huflejt M, Carbone M, Chia D, Goodglick L, Goodman GE, Thornquist MD, Liu G, de Perrot M, Tsao MS, Goparaju C. Fibulin-3 as a blood and effusion biomarker for pleural mesothelioma. N Engl J Med. 2012;367:1417–27. https://doi.org/10.1056/NEJMoa1115050.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  183. Battolla E, Canessa PA, Ferro P, Franceschini MC, Fontana V, Dessanti P, Pinelli V, Morabito A, Fedeli F, Pistillo MP, Roncella S. Comparison of the diagnostic performance of fibulin-3 and mesothelin in patients with pleural effusions from malignant mesothelioma. Anticancer Res. 2017;37:1387–91. https://doi.org/10.21873/anticanres.11460.

    Article  CAS  PubMed  Google Scholar 

  184. Creaney J, Dick IM, Meniawy TM, Leong SL, Leon JS, Demelker Y, Segal A, Musk AW, Lee YC, Skates SJ, Nowak AK, Robinson BW. Comparison of fibulin-3 and mesothelin as markers in malignant mesothelioma. Thorax. 2014;69:895–902. https://doi.org/10.1136/thoraxjnl-2014-205205.

    Article  PubMed  Google Scholar 

  185. Kirschner MB, Pulford E, Hoda MA, Rozsas A, Griggs K, Cheng YY, Edelman JJ, Kao SC, Hyland R, Dong Y, Laszlo V, Klikovits T, Vallely MP, Grusch M, Hegedus B, Dome B, Klepetko W, van Zandwijk N, Klebe S, Reid G. Fibulin-3 levels in malignant pleural mesothelioma are associated with prognosis but not diagnosis. Br J Cancer. 2015;113:963–9. https://doi.org/10.1038/bjc.2015.286.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  186. Ren R, Yin P, Zhang Y, Zhou J, Zhou Y, Xu R, Lin H, Huang C. Diagnostic value of fibulin-3 for malignant pleural mesothelioma: a systematic review and meta-analysis. Oncotarget. 2016;7:84851–9. https://doi.org/10.18632/oncotarget.12707.

    Article  PubMed  PubMed Central  Google Scholar 

  187. Kovac V, Dodic-Fikfak M, Arneric N, Dolzan V, Franko A. Fibulin-3 as a biomarker of response to treatment in malignant mesothelioma. Radiol Oncol. 2015;49:279–85. https://doi.org/10.1515/raon-2015-0019.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  188. Hedman M, Arnberg H, Wernlund J, Riska H, Brodin O. Tissue polypeptide antigen (TPA), hyaluronan and CA 125 as serum markers in malignant mesothelioma. Anticancer Res. 2003;23:531–6.

    CAS  PubMed  Google Scholar 

  189. Schouwink H, Korse CM, Bonfrer JM, Hart AA, Baas P. Prognostic value of the serum tumour markers Cyfra 21-1 and tissue polypeptide antigen in malignant mesothelioma. Lung Cancer. 1999;25:25–32.

    Article  CAS  PubMed  Google Scholar 

  190. Otoshi T, Kataoka Y, Ikegaki S, Saito E, Matsumoto H, Kaku S, Shimada M, Hirabayashi M. Pleural effusion biomarkers and computed tomography findings in diagnosing malignant pleural mesothelioma: a retrospective study in a single center. PLoS One. 2017;12:e0185850. https://doi.org/10.1371/journal.pone.0185850.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  191. Suzuki H, Hirashima T, Kobayashi M, Sasada S, Okamoto N, Uehara N, Tamiya M, Matsuura Y, Morishita N, Kawase I. Cytokeratin 19 fragment/carcinoembryonic antigen ratio in pleural effusion is a useful marker for detecting malignant pleural mesothelioma. Anticancer Res. 2010;30:4343–6.

    PubMed  Google Scholar 

  192. Wang XF, Wu YH, Wang MS, Wang YS. CEA, AFP, CA125, CA153 and CA199 in malignant pleural effusions predict the cause. Asian Pac J Cancer Prev. 2014;15:363–8.

    Article  PubMed  Google Scholar 

  193. Cortes-Dericks L, Schmid RA. CD44 and its ligand hyaluronan as potential biomarkers in malignant pleural mesothelioma: evidence and perspectives. Respir Res. 2017;18:58. https://doi.org/10.1186/s12931-017-0546-5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  194. Creaney J, Dick IM, Segal A, Musk AW, Robinson BW. Pleural effusion hyaluronic acid as a prognostic marker in pleural malignant mesothelioma. Lung Cancer. 2013;82:491–8. https://doi.org/10.1016/j.lungcan.2013.09.016.

    Article  PubMed  Google Scholar 

  195. Grigoriu B, Chahine B, Zerimech F, Gregoire M, Balduyck M, Copin MC, Devos P, Lassalle P, Scherpereel A. Serum mesothelin has a higher diagnostic utility than hyaluronic acid in malignant mesothelioma. Clin Biochem. 2009;42:1046–50.

    Article  CAS  PubMed  Google Scholar 

  196. Mundt F, Nilsonne G, Arslan S, Csuros K, Hillerdal G, Yildirim H, Metintas M, Dobra K, Hjerpe A. Hyaluronan and N-ERC/mesothelin as key biomarkers in a specific two-step model to predict pleural malignant mesothelioma. PLoS One. 2013;8:e72030. https://doi.org/10.1371/journal.pone.0072030.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  197. Johnen G, Gawrych K, Raiko I, Casjens S, Pesch B, Weber DG, Taeger D, Lehnert M, Kollmeier J, Bauer T, Musk AW, Robinson BWS, Bruning T, Creaney J. Calretinin as a blood-based biomarker for mesothelioma. BMC Cancer. 2017;17:386. https://doi.org/10.1186/s12885-017-3375-5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  198. Casjens S, Weber DG, Johnen G, Raiko I, Taeger D, Meinig C, Moebus S, Jockel KH, Bruning T, Pesch B. Assessment of potential predictors of calretinin and mesothelin to improve the diagnostic performance to detect malignant mesothelioma: results from a population-based cohort study. BMJ Open. 2017;7:e017104. https://doi.org/10.1136/bmjopen-2017-017104.

    Article  PubMed  PubMed Central  Google Scholar 

  199. Fiorelli A, Vicidomini G, Di Domenico M, Napolitano F, Messina G, Morgillo F, Ciardiello F, Santini M. Vascular endothelial growth factor in pleural fluid for differential diagnosis of benign and malignant origin and its clinical applications. Interact Cardiovasc Thorac Surg. 2011;12:420–4.

    Article  PubMed  Google Scholar 

  200. Amati M, Tomasetti M, Mariotti L, Tarquini LM, Valentino M, Santarelli L. Assessment of biomarkers in asbestos-exposed workers as indicators of cancer risk. Mutat Res. 2008;655:52–8.

    Article  CAS  PubMed  Google Scholar 

  201. Hirayama N, Tabata C, Tabata R, Maeda R, Yasumitsu A, Yamada S, Kuribayashi K, Fukuoka K, Nakano T. Pleural effusion VEGF levels as a prognostic factor of malignant pleural mesothelioma. Respir Med. 2011;105:137–42.

    Article  PubMed  Google Scholar 

  202. Pattarozzi A, Carra E, Favoni RE, Wurth R, Marubbi D, Filiberti RA, Mutti L, Florio T, Barbieri F, Daga A. The inhibition of FGF receptor 1 activity mediates sorafenib antiproliferative effects in human malignant pleural mesothelioma tumor-initiating cells. Stem Cell Res Ther. 2017;8:119. https://doi.org/10.1186/s13287-017-0573-7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  203. Schelch K, Hoda MA, Klikovits T, Munzker J, Ghanim B, Wagner C, Garay T, Laszlo V, Setinek U, Dome B, Filipits M, Pirker C, Heffeter P, Selzer E, Tovari J, Torok S, Kenessey I, Holzmann K, Grasl-Kraupp B, Marian B, Klepetko W, Berger W, Hegedus B, Grusch M. Fibroblast growth factor receptor inhibition is active against mesothelioma and synergizes with radio- and chemotherapy. Am J Respir Crit Care Med. 2014;190:763–72. https://doi.org/10.1164/rccm.201404-0658OC.

    Article  CAS  PubMed  Google Scholar 

  204. Tamminen JA, Parviainen V, Rönty M, Wohl AP, Murray L, Joenvaara S, Varjosalo M, Leppäranta O, Ritvos O, Sengle G, Renkonen R, Myllärniemi M, Koli K. Gremlin-1 associates with fibrillin microfibrils in vivo and regulates mesothelioma cell survival through transcription factor slug. Oncogene. 2013;2:e66. https://doi.org/10.1038/oncsis.2013.29.

    Article  CAS  Google Scholar 

  205. Yin M, Tissari M, Tamminen J, Ylivinkka I, Ronty M, von Nandelstadh P, Lehti K, Hyytiainen M, Myllarniemi M, Koli K. Gremlin-1 is a key regulator of the invasive cell phenotype in mesothelioma. Oncotarget. 2017;8:98280–97. https://doi.org/10.18632/oncotarget.21550.

    Article  PubMed  PubMed Central  Google Scholar 

  206. Ascoli V, Scalzo CC, Facciolo F, Nardi F. Platelet-derived growth factor receptor immunoreactivity in mesothelioma and nonneoplastic mesothelial cells in serous effusions. Acta Cytol. 1995;39:613–22.

    CAS  PubMed  Google Scholar 

  207. Attanoos RL, Griffin A, Gibbs AR. The use of immunohistochemistry in distinguishing reactive from neoplastic mesothelium. A novel use for desmin and comparative evaluation with epithelial membrane antigen, p53, platelet-derived growth factor-receptor, P-glycoprotein and Bcl-2. Histopathology. 2003;43:231–8.

    Article  CAS  PubMed  Google Scholar 

  208. Filiberti R, Marroni P, Neri M, Ardizzoni A, Betta PG, Cafferata MA, Canessa PA, Puntoni R, Ivaldi GP, Paganuzzi M. Serum PDGF-AB in pleural mesothelioma. Tumour Biol. 2005;26:221–6.

    Article  CAS  PubMed  Google Scholar 

  209. Destro A, Ceresoli GL, Falleni M, Zucali PA, Morenghi E, Bianchi P, Pellegrini C, Cordani N, Vaira V, Alloisio M, Rizzi A, Bosari S, Roncalli M. EGFR overexpression in malignant pleural mesothelioma. An immunohistochemical and molecular study with clinico-pathological correlations. Lung Cancer. 2006;51:207–15. https://doi.org/10.1016/j.lungcan.2005.10.016.

    Article  CAS  PubMed  Google Scholar 

  210. Trupiano J, Geisinger K, Willingham M, Manders P, Zbieranski N, Case D, Levine E. Diffuse malignant mesothelioma of the peritoneum and pleura, analysis of markers. Mod Pathol. 2004;17:476–81.

    Article  PubMed  Google Scholar 

  211. Blanquart C, Gueugnon F, Nguyen JM, Roulois D, Cellerin L, Sagan C, Perigaud C, Scherpereel A, Gregoire M. CCL2, galectin-3, and SMRP combination improves the diagnosis of mesothelioma in pleural effusions. J Thorac Oncol. 2012;7:883–9. https://doi.org/10.1097/JTO.0b013e31824c9272.

    Article  CAS  PubMed  Google Scholar 

  212. Thomas R, Cheah HM, Creaney J, Turlach BA, Lee YC. Longitudinal measurement of pleural fluid biochemistry and cytokines in malignant pleural effusions. Chest. 2016;149:1494–500. https://doi.org/10.1016/j.chest.2016.01.001.

    Article  PubMed  Google Scholar 

  213. Tanaka S, Choe N, Iwagaki A, Hemenway DR, Kagan E. Asbestos exposure induces MCP-1 secretion by pleural mesothelial cells. Exp Lung Res. 2000;26:241–55.

    Article  CAS  PubMed  Google Scholar 

  214. Dragonieri S, van der Schee MP, Massaro T, Schiavulli N, Brinkman P, Pinca A, Carratu P, Spanevello A, Resta O, Musti M, Sterk PJ. An electronic nose distinguishes exhaled breath of patients with malignant pleural mesothelioma from controls. Lung Cancer. 2012;75:326–31. https://doi.org/10.1016/j.lungcan.2011.08.009.

    Article  PubMed  Google Scholar 

  215. de Gennaro G, Dragonieri S, Longobardi F, Musti M, Stallone G, Trizio L, Tutino M. Chemical characterization of exhaled breath to differentiate between patients with malignant plueral mesothelioma from subjects with similar professional asbestos exposure. Anal Bioanal Chem. 2010;398:3043–50.

    Article  PubMed  CAS  Google Scholar 

  216. Cakir Y, Métrailler L, Baumbach JI, Kraus T. Signals in asbestos related diseases in human breath—preliminary results. Int J Ion Mobility Spectrom. 2014;17:87–94. https://doi.org/10.1007/s12127-014-0147-7.

    Article  CAS  Google Scholar 

  217. Chapman EA, Thomas PS, Yates DH. Breath analysis in asbestos-related disorders: a review of the literature and potential future applications. J Breath Res. 2010;4:034001.

    Article  PubMed  CAS  Google Scholar 

  218. Lagniau S, Lamote K, van Meerbeeck JP, Vermaelen KY. Biomarkers for early diagnosis of malignant mesothelioma: do we need another moonshot? Oncotarget. 2017;8:53751–62. https://doi.org/10.18632/oncotarget.17910.

    Article  PubMed  PubMed Central  Google Scholar 

  219. Youssef O, Sarhadi VK, Armengol G, Piirilä P, Knuuttila A, Knuutila S. Exhaled breath condensate as a source of biomarkers for lung carcinomas. A focus on genetic and epigenetic markers-a mini-review. Genes Chromosomes Cancer. 2016;55:905–14. https://doi.org/10.1002/gcc.22399.

    Article  CAS  PubMed  Google Scholar 

  220. Youssef O, Knuuttila A, Piirilä P, Böhling T, Sarhadi V, Knuutila S. Hotspot mutations detectable by next-generation sequencing in exhaled breath condensates from patients with lung cancer. Anticancer Res. 2018;38:5627–34. https://doi.org/10.21873/anticanres.12897.

    Article  CAS  PubMed  Google Scholar 

  221. Youssef O, Knuuttila A, Piirilä P, Böhling T, Sarhadi V, Knuutila S. Presence of cancer-associated mutations in exhaled breath condensates of healthy individuals by next generation sequencing. Oncotarget. 2017;8:18166–76. https://doi.org/10.18632/oncotarget.15233.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

We are grateful to Ewen MacDonald PhD for the correction of grammar and style. Financial support from Sigrid Jusélius Foundation is gratefully acknowledged.

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  1. Occupational Safety, Finnish Institute of Occupational Health, Helsinki, Finland

    Eeva Kettunen

  2. Department of Pathology, Faculty of Medicine, The University of Helsinki, Helsinki, Finland

    Sakari Knuutila & Virinder Sarhadi

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  1. Department of Pathology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland

    Sisko Anttila

  2. Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Paolo Boffetta

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Kettunen, E., Knuutila, S., Sarhadi, V. (2020). Malignant Mesothelioma: Molecular Markers. In: Anttila, S., Boffetta, P. (eds) Occupational Cancers. Springer, Cham. https://doi.org/10.1007/978-3-030-30766-0_18

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