Advertisement

Exploring Potential of RPPA Technique in Oral Cancer Biomarker Discovery Research

  • Neera Singh
  • Sanghamitra PatiEmail author
Chapter

Abstract

Oral squamous cell carcinoma (OSCC) is one of the leading causes of cancer-related mortality worldwide. India has one of the highest incidence rates of oral cancer due to extremely popular use of different forms of smokeless tobacco like areca-nut and betel-leaf chewing habits. Delayed detection is one of the major contributing factors for higher morbidity rate among oral cancer patients. Despite new innovations in surgery, radiation, and chemotherapy, the prognosis for OSCC patients remains poor, with the lowest 5-year survival rate (40–50%). Presently, there are no effective molecular markers available for earlier screening of oral cancer. The gold standard for diagnosis of OSCC is the conventional oral examination followed by histopathological analysis of biopsy from the suspicious lesions. Detection of cancerous lesions by invasive method like biopsy is often associated with patient discomfort and reluctance for further follow-ups. Therefore, it is critical to develop non-invasive diagnostic methods for earlier screening of oral cancers for improved survival rate. In complex disorders like cancer, genetic alterations do not always correlate with the disease causes. Changes in protein structure and expression levels play an important role in tumor development and progression. Thus, undoubtedly proteins are attractive molecular targets as potential biomarkers due to the fact that they participate more actively in cellular activities than DNA and RNA. Proteomics holds a great promise for the discovery of proteins that may be used as biomarkers for the early detection of various cancers. Salivary diagnostics is a rapidly advancing field that offers clinicians and patients the potential of rapid, noninvasive diagnostics with excellent accuracy. The chapter describes various proteomics approaches utilized for the biomarker discovery of oral cancer in both tissues and saliva with a special focus on application of Reverse Phase protein array (RPPA) in oral cancer. RPPA is a novel, high throughput technique that can perform robust quantification using nanolitres of protein lysates. RPPA being a highly sensitive and specific technique has been successfully used in biomarker discovery, personalized therapy and to study differential protein expression pattern and post-translational modifications in various cancers.

Keywords

Oral cancer RPPA Protein Biomarker Diagnosis 

References

  1. 1.
    Torre LA, Siegel RL, Ward EM, Jemal A. Global cancer incidence and mortality rates and trends—an update. Cancer Epidemiol Biomark Prev. 2016;25:16–27.  https://doi.org/10.1158/1055-9965.EPI-15-0578.CrossRefGoogle Scholar
  2. 2.
    Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136:E359–86.  https://doi.org/10.1002/ijc.29210.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Petersen PE. Oral cancer prevention and control—the approach of the World Health Organization. Oral Oncol. 2009;45:454–60.  https://doi.org/10.1016/j.oraloncology.2008.05.023.CrossRefPubMedGoogle Scholar
  4. 4.
    Fukuda M, Kusama K, Sakashita H. Molecular insights into the proliferation and progression mechanisms of the oral cancer: strategies for the effective and personalized therapy. Jpn Dent Sci Rev. 2012;48:23–41.  https://doi.org/10.1016/j.jdsr.2011.08.001.CrossRefGoogle Scholar
  5. 5.
    Mangalath U, Aslam S, Kooliyat AH, Khader A, Francis PG, Mikacha SK, et al. Recent trends in prevention of oral cancer. J Int Prev Commun Dent. 2014;4:S131–8.  https://doi.org/10.4103/2231-0762.149018.CrossRefGoogle Scholar
  6. 6.
    Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646–74.  https://doi.org/10.1016/j.cell.2011.02.013.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Sethi S, Ali S, Philip PA, Sarkar FH. Clinical advances in molecular biomarkers for cancer diagnosis and therapy. Int J Mol Sci. 2013;14:14771–84.  https://doi.org/10.3390/ijms140714771.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Strimbu K, Tavel JA. What are biomarkers? Curr Opin HIV AIDS. 2010;5:463–6.  https://doi.org/10.1097/COH.0b013e32833ed177.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    William B, Ronald BH. Characteristics of the ideal tumor marker in Hollandfrei cancer medicine. 6th ed. Hamilton: BC, Decker; 2003.Google Scholar
  10. 10.
    Carr KM, Rosenblatt K, Petricoin EF, Liotta LA. Genomic and proteomic approaches for studying human cancer: prospects for true patient-tailored therapy. Hum Genomics. 2004;1:134–40.  https://doi.org/10.1186/1479-7364-1-2-134.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Shruthi BS, Vinodhkumar P, Selvamani. Proteomics: a new perspective for cancer. Adv Biomed Res. 2016;5:67.  https://doi.org/10.4103/2277-9175.180636.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Gallagher RI, Espina V. Reverse phase protein arrays: mapping the path towards personalized medicine. Mol Diagn Ther. 2014;18:619–30.  https://doi.org/10.1007/s40291-014-0122-3.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Maes E, Mertens I, Valkenborg D, Pauwels P, Rolfo C, Baggerman G. Proteomics in cancer research: are we ready for clinical practice? Crit Rev Oncol Hematol. 2015;96:437–48.  https://doi.org/10.1016/j.critrevonc.2015.07.006.CrossRefPubMedGoogle Scholar
  14. 14.
    Hudler P, Kocevar N, Komel R. Proteomic approaches in biomarker discovery: new perspectives in cancer diagnostics. Sci World J. 2014;2014:260348.  https://doi.org/10.1155/2014/260348.CrossRefGoogle Scholar
  15. 15.
    Mordente A, Meucci E, Martorana GE, Silvestrini A. Cancer biomarkers discovery and validation: state of the art, problems and future perspectives. Adv Exp Med Biol. 2015;867:9–26.  https://doi.org/10.1007/978-94-017-7215-0_2.CrossRefPubMedGoogle Scholar
  16. 16.
    Parker CE, Borchers CH. Mass spectrometry based biomarker discovery, verification, and validation—quality assurance and control of protein biomarker assays. Mol Oncol. 2014;8:840–58.  https://doi.org/10.1016/j.molonc.2014.03.006.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Masuda M, Yamada T. Signaling pathway profiling using reverse-phase protein array and its clinical applications. Expert Rev Proteomics. 2017;14:607–15.  https://doi.org/10.1080/14789450.2017.1344101.CrossRefPubMedGoogle Scholar
  18. 18.
    Paweletz CP, Charboneau L, Bichsel VE, Simone NL, Chen T, Gillespie JW, et al. Reverse phase protein microarrays which capture disease progression show activation of pro-survival pathways at the cancer invasion front. Oncogene. 2001;20:1981–9.  https://doi.org/10.1038/sj.onc.1204265.CrossRefPubMedGoogle Scholar
  19. 19.
    Mueller C, Liotta LA, Espina V. Reverse phase protein microarrays advance to use in clinical trials. Mol Oncol. 2010;4:461–81.  https://doi.org/10.1016/j.molonc.2010.09.003.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Huang Y, Zhu H. Protein array-based approaches for biomarker discovery in cancer. Genomics Proteomics Bioinformatics. 2017;15:73–81.  https://doi.org/10.1016/j.gpb.2017.03.001.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Tanase C, Albulescu R, Neagu M. Proteomic approaches for biomarker panels in cancer. J Immunoassay Immunochem. 2016;37:1–15.  https://doi.org/10.1080/15321819.2015.1116009.CrossRefPubMedGoogle Scholar
  22. 22.
    Wachter A, Bernhardt S, Beissbarth T, Korf U. Analysis of reverse phase protein array data: from experimental design towards targeted biomarker discovery. Microarrays. 2015;4:520–39.  https://doi.org/10.3390/microarrays4040520.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Akbani R, Becker KF, Carragher N, Goldstein T, de Koning L, Korf U, et al. Realizing the promise of reverse phase protein arrays for clinical, translational, and basic research: a workshop report: the RPPA (Reverse Phase Protein Array) Society. Mol Cell Proteomics. 2014;13:1625–43.  https://doi.org/10.1074/mcp.O113.034918.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Chen Y, Azman SN, Kerishnan JP, Zain RB, Chen YN, Wong Y-L, et al. Identification of host-immune response protein candidates in the sera of human oral squamous cell carcinoma patients. PLoS One. 2014;9:e109012.  https://doi.org/10.1371/journal.pone.0109012.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Chen B, Liu Y, Shen Y, Xia Z, He G, Liang S. Protein microarrays in proteome-wide applications. J Proteomics Bioinform. 2014;S12:001.  https://doi.org/10.4172/jpb.S12-001.CrossRefGoogle Scholar
  26. 26.
    Creighton CJ, Huang S. Reverse phase protein arrays in signaling pathways: a data integration perspective. Drug Des Devel Ther. 2015;9:3519–27.  https://doi.org/10.2147/DDDT.S38375.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Ni YH, Ding L, Hu QG, Hua ZC. Potential biomarkers for oral squamous cell carcinoma: proteomics discovery and clinical validation. Proteomics Clin Appl. 2015;9:86–97.  https://doi.org/10.1002/prca.201400091.CrossRefPubMedGoogle Scholar
  28. 28.
    Sawant S, Vaidya M, Chaukar D, Alam H, Dmello C, Gangadaran P, et al. Clinical significance of aberrant vimentin expression in oral premalignant lesions and carcinomas. Oral Dis. 2014;20(5):453–65.  https://doi.org/10.1111/odi.12151.CrossRefPubMedGoogle Scholar
  29. 29.
    Kaur J, Jacobs R, Huang Y, Salvo N, Politis C. Salivary biomarkers for oral cancer and pre-cancer screening: a review. Clin Oral Investig. 2018;22:633–40.  https://doi.org/10.1007/s00784-018-2337-x.CrossRefPubMedGoogle Scholar
  30. 30.
    Dey KK, Pal I, Bharti R, Dey G, Kumar BN, Rajput S, et al. Identification of RAB2A and PRDX1 as the potential biomarkers for oral squamous cell carcinoma using mass spectrometry-based comparative proteomic approach. Tumour Biol. 2015;36:9829–37.  https://doi.org/10.1007/s13277-015-3758-7.CrossRefPubMedGoogle Scholar
  31. 31.
    Huang TT, Chen JY, Tseng CE, Su YC, Ho HC, Lee MS, et al. Decreased GRP78 protein expression is a potential prognostic marker of oral squamous cell carcinoma in Taiwan. J Formos Med Assoc. 2010;109: 326–37. doi: 10.1016/S0929-6646(10)60060-5.Google Scholar
  32. 32.
    Rivera C, Oliveira AK, Costa RAP, De Rossi T, Paes Leme AF. Prognostic biomarkers in oral squamous cell carcinoma: a systematic review. Oral Oncol. 2017;72:38–47.CrossRefGoogle Scholar
  33. 33.
    Chai YD, Zhang L, Yang Y, Su T, Charugundla P, Ai J, et al. Discovery of potential serum protein biomarkers for lymph node metastasis in oral cancer. Head Neck. 2016;38:118–25.  https://doi.org/10.1002/hed.23870.CrossRefPubMedGoogle Scholar
  34. 34.
    Rai V, Mukherjee R, Ghosh AK, Routray A, Chakraborty C. “Omics” in oral cancer: new approaches for biomarker discovery. Arch Oral Biol. 2018;87:15–34.  https://doi.org/10.1016/j.archoralbio.2017.12.003.CrossRefPubMedGoogle Scholar
  35. 35.
    Arellano-Garcia ME, Li R, Liu X, Xie Y, Yan X, Loo JA, et al. Identification of tetranectin as a potential biomarker for metastatic oral cancer. Int J Mol Sci. 2010;11:3106–21.  https://doi.org/10.3390/ijms11093106.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Bhattarai BP, Klongnoi B, Khovidhunkit SP, Wongsirichat, Natthamet. Protein biomarker in saliva in oral squamous cell carcinoma. SWU Dent J. 2017;10:13. https://www.researchgate.net/publication/322832732_protein_biomarker_in_saliva_in_oral_squamous_cell_carcinoma. Accessed 20 Mar 2018.
  37. 37.
    Wu CC, Chu HW, Hsu CW, Chang KP, Liu HP. Saliva proteome profiling reveals potential salivary biomarkers for detection of oral cavity squamous cell carcinoma. Proteomics. 2015;15:3394–404.  https://doi.org/10.1002/pmic.201500157.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.DBT-BioCARE Women Scientist, Institute of Life SciencesBhubaneswarIndia
  2. 2.Department of Health Research, Government of IndiaICMR Regional Medical Research CentreBhubaneswarIndia

Personalised recommendations