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Identification of potential serum markers for endometrial cancer using protein expression profiling

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Abstract

Objectives

Screening method of endometrial cancer (EC) has not been established yet. Our study was to explore serum biomarkers of EC patients using surface-enhanced laser desorption and ionization-time-of-flight mass spectrometry (SELDI-TOF MS).

Methods

Serum samples from 65 EC patients and 40 controls were analyzed by SELDI-TOF MS (training set). Single- and multi-variant analyses were performed to compare protein profiles in serum of EC patients and healthy controls. Subsequently, blind test set including 40 EC patients and 40 controls were analyzed for validation.

Results

A panel of four biomarker candidates were selected in training set analysis. These markers could also distinguish stage I patients from controls. Among them, two biomarkers were purified and identified as apolipoprotein A1 and a modified form of apolipoprotein C1. Screening for blind test set using dual-biomarker analysis yielded a sensitivity of 82% and a specificity of 86%.

Conclusions

Involvement of apolipoproteins with EC is first suggested in this study. In addition to possibility of screening method for EC, findings of these new biomarkers might be related with carcinogenesis or predisposition to EC.

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References

  • Amant F, Moerman P, Neven P, Timmerman D, Van Limbergen E, Vergote I (2006) Endometrial cancer. Lancet 366:491–505

    Article  Google Scholar 

  • Chang SJ, Hou MF, Tsai SM, Wu SH, Hou LA, Ma H, Shann TY, Wu SH, Tsai LY (2007) The association between lipid profiles and breast cancer among Taiwanese women. Clin Chem Lab Med 45:1219–1223

    Article  CAS  PubMed  Google Scholar 

  • Cherchi PL, Dessole S, Ruiu GA, Ambrosini G, Farina M, Capobianco G, Ambrosini A (1999) The value of serum CA 125 and association CA 125/CA 19-9 in endometrial carcinoma. Eur J Gynaecol Oncol 20:315–317

    CAS  PubMed  Google Scholar 

  • Coussens LM, Werb Z (2002) Inflammation and cancer. Nature 420:860–867

    Article  CAS  PubMed  Google Scholar 

  • Ehmann M, Felix K, Hartmann D, Schnölzer M, Nees M, Vorderwülbecke S, Bogumil R, Büchler MW, Friess H (2007) Identification of potential markers for the detection of pancreatic cancer through comparative serum protein expression profiling. Pancreas 34:205–214

    Article  CAS  PubMed  Google Scholar 

  • Emoto M, Tamura R, Shirota K, Hachisuga T, Kawarabayashi T (2002) Clinical usefulness of color Doppler ultrasound in patients with endometrial hyperplasia and carcinoma. Cancer 94:700–706

    Article  PubMed  Google Scholar 

  • Enomoto T, Fujita M, Inoue M, Nomura T (1995) Shroyer KR (1995) Alteration of the p53 tumor suppressor gene and activation of c-K-ras-2 protooncogene in endometrial adenocarcinoma from Colorado. Am J Clin Pathol 103:224–230

    CAS  PubMed  Google Scholar 

  • Feng YZ, Shiozawa T, Horiuchi A, Shih HC, Miyamoto T, Kashima H, Suzuki A, Nikaido T, Konishi I (2005) Intratumoral heterogeneous expression of p53 correlates with p53 mutation, Ki-67, and cyclin A expression in endometrioid-type endometrial adenocarcinomas. Virchows Arch 447:816–822

    Article  CAS  PubMed  Google Scholar 

  • Gadducci A, Cosio S, Carpi A, Nicolini A, Genazzani AR (2004) Serum tumor markers in the management of ovarian, endometrial and cervical cancer. Biomed Pharmacother 58:24–38

    Article  CAS  PubMed  Google Scholar 

  • Gadomska H, Grzechocińska B, Janecki J, Nowicka G, Powolny M, Marianowski L (2005) Serum lipids concentration in women with benign and malignant ovarian tumours. Eur J Obstet Gynecol Reprod Biol 120:87–90

    Article  CAS  PubMed  Google Scholar 

  • Guo J, Yang EC, Desouza L, Diehl G, Rodrigues MJ, Romaschin AD, Colgan TJ, Siu KW (2005) A strategy for high-resolution protein identification in surface-enhanced laser desorption/ionization mass spectrometry: calgranulin A and chaperonin 10 as protein markers for endometrial carcinoma. Proteomics 5:1953–1966

    Article  CAS  PubMed  Google Scholar 

  • Huang HL, Stasyk T, Morandell S, Dieplinger H, Falkensammer G, Griesmacher A, Mogg M, Schreiber M, Feuerstein I, Huck CW, Stecher G, Bonn GK, Huber LA (2006) Biomarker discovery in breast cancer serum using 2-D differential gel electrophoresis/MALDI-TOF/TOF and data validation by routine clinical assays. Electrophoresis 27:1641–1650

    Article  CAS  PubMed  Google Scholar 

  • Jacobs I, Bast RC Jr (1987) The elevation of CA 125 tumor-associated antigen: a review of the literature. Hum Reprod 4:1–12

    Google Scholar 

  • Kanamori Y, Kigawa J, Itamochi H, Shimada M, Takahashi M, Kamazawa S, Sato S, Akeshima R, Terakawa N (2001) Correlation between loss of PTEN expression and Akt phosphorylation in endometrial carcinoma. Clin Cancer Res 7:892–895

    CAS  PubMed  Google Scholar 

  • Kanamori Y, Kigawa J, Itamochi H, Sultana H, Suzuki M, Ohwada M, Kamura T, Sugiyama T, Kikuchi Y, Kita T, Fujiwara K, Terakawa N (2002) PTEN expression is associated with prognosis for patients with advanced endometrial carcinoma undergoing postoperative chemotherapy. Int J Cancer 100:686–689

    Article  CAS  PubMed  Google Scholar 

  • Kolasa IK, Rembiszewska A, Janiec-Jankowska A, Dansonka-Mieszkowska A, Lewandowska AM, Konopka B, Kupryjańczyk J (2006) PTEN mutation, expression and LOH at its locus in ovarian carcinomas. Relation to TP53, K-RAS and BRCA1 mutations. Gynecol Oncol 103:692–697

    Article  CAS  PubMed  Google Scholar 

  • Kozak KR, Su F, Whitelegge JP, Faull K, Reddy S, Farias-Eisner R (2005) Characterization of serum biomarkers for detection of early stage ovarian cancer. Proteomics 5:4589–4596

    Article  CAS  PubMed  Google Scholar 

  • Lagarda H, Catasus L, Arguelles R, Matias-Guiu X, Prat J (2001) K-ras mutations in endometrial carcinomas with microsatellite instability. J Pathol 193:193–199

    Article  CAS  PubMed  Google Scholar 

  • Lax SF, Kendall B, Tashiro H, Slebos RJ, Hedrick L (2000) The frequency of p53, K-ras mutations, and microsatellite instability differs in uterine endometrioid and serous carcinoma: evidence of distinct molecular genetic pathways. Cancer 88:814–824

    Article  CAS  PubMed  Google Scholar 

  • Minagawa Y, Sato S, Ito M, Onohara Y, Nakamoto S, Kigawa J (2005) Transvaginal ultrasonography and endometrial cytology as a diagnostic schema for endometrial cancer. Gynecol Obstet Invest 59:149–154

    Article  PubMed  Google Scholar 

  • Mizumoto Y, Kyo S, Mori N, Sakaguchi J, Ohno S, Maida Y, Hashimoto M, Takakura M, Inoue M (2007) Activation of ERK1/2 occurs independently of KRAS or BRAF status in endometrial cancer and is associated with favorable prognosis. Cancer Sci 98:652–658

    Article  CAS  PubMed  Google Scholar 

  • Moore LE, Fung ET, McGuire M, Rabkin CC, Molinaro A, Wang Z, Zhang F, Wang J, Yip C, Meng XY, Pfeiffer RM (2006) Evaluation of apolipoprotein A1 and posttranslationally modified forms of transthyretin as biomarkers for ovarian cancer detection in an independent study population. Cancer Epidemiol Biomarkers Prev 15:1641–1646

    Article  CAS  PubMed  Google Scholar 

  • Mori N, Kyo S, Sakaguchi J, Mizumoto Y, Ohno S, Maida Y, Hashimoto M, Takakura M, Inoue M (2007) Concomitant activation of AKT with extracellular-regulated kinase 1/2 occurs independently of PTEN or PIK3CA mutations in endometrial cancer and may be associated with favorable prognosiss. Cancer Sci 98:1881–1888

    Article  CAS  PubMed  Google Scholar 

  • Mutter GL, Lin MC, Fitzgerald JT, Kum JB, Baak JP, Lees JA, Weng LP (2000) Eng C (2000) Altered PTEN expression as a diagnostic marker for the earliest endometrial precancers. J Natl Cancer Inst 92:924–930

    Article  CAS  PubMed  Google Scholar 

  • Mutter GL, Ince TA, Baak JP, Kust GA, Zhou XP, Eng C (2001) Molecular identification of latent precancers in histologically normal endometrium. Cancer Res 61:4311–4314

    CAS  PubMed  Google Scholar 

  • Navab M, Yu R, Gharavi N, Huang W, Ezra N, Lotfizadeh A, Anantharamaiah GM, Alipour N, Van Lenten BJ, Reddy ST, Marelli D (2007) High-density lipoprotein: antioxidant and anti-inflammatory properties. Curr Atheroscler Rep 9:244–248

    Article  CAS  PubMed  Google Scholar 

  • Salvesen HB, Stefansson I, Kretzschmar EI, Gruber P, MacDonald ND, Ryan A, Jacobs IJ, Akslen LA, Das S (2004) Significance of PTEN alterations in endometrial carcinoma: a population-based study of mutations, promoter methylation and PTEN protein expression. Int J Oncol 25:1615–1623

    CAS  PubMed  Google Scholar 

  • Sato N, Fukushima N, Chang R, Matsubayashi H, Goggins M (2006) Differentialand epigenetic gene expression profiling identifies frequent disruption of the RELN pathway in pancreatic cancers. Gastroenterology 130:548–565

    Article  CAS  PubMed  Google Scholar 

  • Shang Y (2006) Molecular mechanisms of oestrogen and SERMs in endometrial carcinogenesis. Nat Rev Cancer 6:360–368

    Article  CAS  PubMed  Google Scholar 

  • Tabor A, Watt HC, Wald NJ (2002) Endometrial thickness as a test for endometrial cancer in women with postmenopausal vaginal bleeding. Obstet Gynecol 99:663–670

    Article  PubMed  Google Scholar 

  • Takano S, Yoshitomi H, Togawa A, Sogawa K, Shida T, Kimura F, Shimizu H, Tomonaga T, Nomura F, Miyazaki M (2008) Apolipoprotein C-1 maintains cell survival by preventing from apoptosis in pancreatic cancer cells. Oncogene 27:2810–2822

    Article  CAS  PubMed  Google Scholar 

  • Velasco A, Bussaglia E, Pallares J, Dolcet X, Llobet D, Encinas M, Llecha N, Palacios J, Prat J, Matias-Guiu X (2006) PIK3CA gene mutations in endometrial carcinoma: correlation with PTEN and K-RAS alterations. Hum Pathol 37:1465–1472

    Article  CAS  PubMed  Google Scholar 

  • Yang EC, Guo J, Diehl G, DeSouza L, Rodrigues MJ, Romaschin AD, Colgan TJ, Siu KW (2004) Protein expression profiling of endometrial malignancies reveals a new tumor marker: chaperonin 10. J Proteome Res 3:636–643

    Article  CAS  PubMed  Google Scholar 

  • Yoshizaki T, Enomoto T, Nakashima R, Ueda Y, Kanao H, Yoshino K, Fukumoto M, Yoneda Y, Buzard GS, Murata Y (2005) Altered protein expression in endometrial carcinogenesis. Cancer Lett 226:101–106

    Article  CAS  PubMed  Google Scholar 

  • Zhang Z, Bast RC Jr, Yu Y, Li J, Sokoll LJ, Rai AJ, Rosenzweig JM, Cameron B, Wang YY, Meng XY, Berchuck A, Van Haaften-Day C, Hacker NF, de Bruijn HW, van der Zee AG, Jacobs IJ, Fung ET, Chan DW (2004) Three biomarkers identified from serum proteomic analysis for the detection of early stage ovarian cancer. Cancer Res 64:5882–5890

    Article  CAS  PubMed  Google Scholar 

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We declare that we have no conflict of interest.

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Correspondence to Yoshihiro Kikuchi.

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Takano, M., Kikuchi, Y., Asakawa, T. et al. Identification of potential serum markers for endometrial cancer using protein expression profiling. J Cancer Res Clin Oncol 136, 475–481 (2010). https://doi.org/10.1007/s00432-009-0680-7

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  • DOI: https://doi.org/10.1007/s00432-009-0680-7

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