Skip to main content

Advertisement

Log in

Cancer-Testis Antigens as New Candidate Diagnostic Biomarkers for Transitional Cell Carcinoma of Bladder

  • Original Article
  • Published:
Pathology & Oncology Research

Abstract

To evaluate the diagnostic potential of 23 candidate genes, belonging to a category of tumor-specific antigens known as cancer-testis antigens (CTAs), in transitional cell carcinoma (TCC) patients. The expression of 16 known candidate CTAs and seven testis restricted/selective genes, predominantly expressed in the testis, was evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR). Urinary exfoliated cells (UECs) and cancerous tissues of 73 TCC patients were used as cases, while 25 tumor-free adjacent bladder tissue specimens along with bladder tissue specimens and UECs of five non-TCC individuals were analyzed as controls. Among the known CTAs only MAGEA3, MAGEB4, TSGA10, PIWIL2, OIP5, and ODF4 were expressed specifically in TCC tissues and UEC samples. ACTL7A, AURKC, and CGB2 were testis-restricted/selective genes that indicated specific expression in cases in comparison to controls. MAGEA3, MAGEB4, and ODF4 mRNA was detectable in more than 50% of both TCC tissues, and UEC samples. Slight differences were detected in the mRNA expression pattern of candidate genes between the UEC samples and tumor tissues. Different panels formed by combinations of these genes can show up to 95.9% and 94.5% of positivity in TCC tissues and UEC samples, respectively, suggesting their diagnostic and surveillance potential. Meanwhile the RT-PCR assay of at least MAGEA3, MAGEB4, and ODF4 may be particularly useful for diagnostic and surveillance of TCC in the form of a multi-biomarker panel.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A (2015) Global cancer statistics, 2012. CA Cancer J Clin 65(2):87–108

    Article  PubMed  Google Scholar 

  2. Masoompour SM, Yarmohammadi H, Rezaianzadeh A, Lankarani KB (2011) Cancer incidence in southern Iran, 1998–2002: results of population-based cancer registry. Cancer Epidemiol 35(5):e42–e47

    Article  PubMed  Google Scholar 

  3. Babjuk M, Burger M, Zigeuner R, Shariat SF, van Rhijn BWG, Compérat E, Sylvester RJ, Kaasinen E, Böhle A, Palou Redorta J, Rouprêt M (2013) EAU guidelines on non–muscle-invasive urothelial carcinoma of the bladder: update 2013. Eur Urol 64(4):639–653. https://doi.org/10.1016/j.eururo.2013.06.003

    Article  Google Scholar 

  4. Lotan Y, Svatek RS, Malats N (2008) Screening for bladder cancer: a perspective. World J Urol 26:13–18

    Article  PubMed  Google Scholar 

  5. Turco P, Houssami N, Bulgaresi P, Troni GM, Galanti L, Cariaggi MP, Cifarelli P, Crocetti E, Ciatto S (2011) Is conventional urinary cytology still reliable for diagnosis of primary bladder carcinoma? Accuracy based on data linkage of a consecutive clinical series and cancer registry. Acta Cytol 55(2):193–196. https://doi.org/10.1159/000320861

    Article  PubMed  Google Scholar 

  6. Simpson AJ, Caballero OL, Jungbluth A, Chen YT, Old LJ (2005) Cancer/testis antigens, gametogenesis and cancer. Nat Rev Cancer 5(8):615–625. https://doi.org/10.1038/nrc1669

    Article  CAS  PubMed  Google Scholar 

  7. Caballero OL, Chen YT (2009) Cancer/testis (CT) antigens: potential targets for immunotherapy. Cancer Sci 100(11):2014–2021. https://doi.org/10.1111/j.1349-7006.2009.01303.x8

    Article  CAS  PubMed  Google Scholar 

  8. Scanlan MJ, Gordon CM, Williamson B, Lee SY, Chen YT, Stockert E, Jungbluth A, Ritter G, Jäger D, Jäger E (2002) Identification of cancer/testis genes by database mining and mRNA expression analysis. Int J Cancer 98(4):485–492

    Article  CAS  PubMed  Google Scholar 

  9. Scanlan MJ, Simpson AJ, Old LJ (2004) The cancer/testis genes: review, standardization, and commentary. Cancer Immun 4:1

    PubMed  Google Scholar 

  10. Sharma P, Shen Y, Wen S, Bajorin DF, Reuter VE, Old LJ, Jungbluth AA (2006) Cancer-testis antigens: expression and correlation with survival in human urothelial carcinoma. Clin Cancer Res 12(18):5442–5447. https://doi.org/10.1158/1078–0432.ccr-06-0527

    Article  CAS  PubMed  Google Scholar 

  11. Zamuner FT, Karia BT, de Oliveira CZ, Santos CR, Carvalho AL, Vettore AL (2015) A comprehensive expression analysis of cancer testis antigens in head and neck squamous cell carcinoma revels MAGEA3/6 as a marker for recurrence. Mol Cancer Ther 14(3):828–834. https://doi.org/10.1158/1535–7163.mct-14-0796

    Article  CAS  PubMed  Google Scholar 

  12. Bellati F, Napoletano C, Tarquini E, Palaia I, Landi R, Manci N, Spagnoli G, Rughetti A, Panici PB, Nuti M (2007) Cancer testis antigen expression in primary and recurrent vulvar cancer: association with prognostic factors. Eur J Cancer 43(17):2621–2627. https://doi.org/10.1016/j.ejca.2007.08.031

    Article  CAS  PubMed  Google Scholar 

  13. Bar-Haim E, Paz A, Machlenkin A, Hazzan D, Tirosh B, Carmon L, Brenner B, Vadai E, Mor O, Stein A (2004) MAGE-A8 overexpression in transitional cell carcinoma of the bladder: identification of two tumour-associated antigen peptides. Br J Cancer 91(2):398–407

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Fradet Y, Picard V, Bergeron A, LaRue H (2005) Cancer-testis antigen expression in bladder cancer. Prog Urol 15(6 Suppl 1):1303–1313

    PubMed  Google Scholar 

  15. Picard V, Bergeron A, Larue H, Fradet Y (2007) MAGE-A9 mRNA and protein expression in bladder cancer. Int J Cancer 120(10):2170–2177. https://doi.org/10.1002/ijc.22282

    Article  CAS  PubMed  Google Scholar 

  16. Bergeron A, Picard V, LaRue H, Harel F, Hovington H, Lacombe L, Fradet Y (2009) High frequency of MAGE-A4 and MAGE-A9 expression in high-risk bladder cancer. Int J Cancer 125(6):1365–1371

    Article  CAS  PubMed  Google Scholar 

  17. Dyrskjot L, Zieger K, Kissow Lildal T, Reinert T, Gruselle O, Coche T, Borre M, Orntoft TF (2012) Expression of MAGE-A3, NY-ESO-1, LAGE-1 and PRAME in urothelial carcinoma. Br J Cancer 107(1):116–122. https://doi.org/10.1038/bjc.2012.215

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Yin B, Liu G, Wang XS, Zhang H, Song YS, Wu B (2012) Expression profile of cancer-testis genes in transitional cell carcinoma of the bladder. Urol Oncol 30(6):886–892. https://doi.org/10.1016/j.urolonc.2010.08.017

    Article  CAS  PubMed  Google Scholar 

  19. Mengus C, Schultz-Thater E, Coulot J, Kastelan Z, Goluza E, Coric M, Spagnoli GC, Hudolin T (2013) MAGE-A10 cancer/testis antigen is highly expressed in high-grade non-muscle-invasive bladder carcinomas. Int J Cancer 132(10):2459–2463. https://doi.org/10.1002/ijc.27914

    Article  CAS  PubMed  Google Scholar 

  20. Kawai T, Enomoto Y, Morikawa T, Matsushita H, Kume H, Fukayama M, Yamaguchi H, Kakimi K, Homma Y (2014) High expression of heat shock protein 105 predicts a favorable prognosis for patients with urinary bladder cancer treated with radical cystectomy. Mol Clin Oncol 2(1):38–42. https://doi.org/10.3892/mco.2013.203

    Article  PubMed  Google Scholar 

  21. Hofmann O, Caballero OL, Stevenson BJ, Chen YT, Cohen T, Chua R, Maher CA, Panji S, Schaefer U, Kruger A, Lehvaslaiho M, Carninci P, Hayashizaki Y, Jongeneel CV, Simpson AJ, Old LJ, Hide W (2008) Genome-wide analysis of cancer/testis gene expression. Proc Natl Acad Sci U S A 105(51):20422–20427. https://doi.org/10.1073/pnas.0810777105

    Article  PubMed  PubMed Central  Google Scholar 

  22. Eble J, Sauter G, Epstein J, Sesterhenn I (2004) World Health Organization classification of tumors. Tumors of the urinary system and genital organs. IARC Press, Lyon, Pathology and Genetics

    Google Scholar 

  23. Patard JJ, Brasseur F, Gil-Diez S, Radvanyi F, Marchand M, Francois P, Abi-Aad A, Van Cangh P, Abbou CC, Chopin D et al (1995) Expression of MAGE genes in transitional-cell carcinomas of the urinary bladder. Int J Cancer 64(1):60–64

    Article  CAS  PubMed  Google Scholar 

  24. Katayama H, Brinkley WR, Sen S (2003) The Aurora kinases: role in cell transformation and tumorigenesis. Cancer Metastasis Rev 22(4):451–464

    Article  PubMed  Google Scholar 

  25. Wang J, Liu X, Dou Z, Chen L, Jiang H, Fu C, Fu G, Liu D, Zhang J, Zhu T (2014) Mitotic regulator Mis18β interacts with and specifies the centromeric assembly of molecular chaperone holliday junction recognition protein (HJURP). J Biol Chem 289(12):8326–8336

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Mansouri K, Mostafie A, Rezazadeh D, Shahlaei M, Modarressi MH (2016) New function of TSGA10 gene in angiogenesis and tumor metastasis: a response to a challengeable paradox. Hum Mol Genet 25(2):233–244

    Article  CAS  PubMed  Google Scholar 

  27. Yang B, O'Herrin SM, Wu J, Reagan-Shaw S, Ma Y, Bhat KM, Gravekamp C, Setaluri V, Peters N, Hoffmann FM (2007) MAGE-A, mMage-b, and MAGE-C proteins form complexes with KAP1 and suppress p53-dependent apoptosis in MAGE-positive cell lines. Cancer Res 67(20):9954–9962

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Sincere gratitude and appreciation to Dr. R Glen Calderhead who thoroughly copyedited our manuscript for language usage, spelling, and grammar. We are also thankful to Mrs. Harieh Rasouli, Mrs. Soheila Khamseh, Mr. Esmaeel Khoshbakht, and Mr. Saeed Farabi who kindly helped us during the sampling process.

Funding

The research reported in this manuscript has been fully funded by the Cancer Research Center of Tehran Medical Sciences University under reference number 93–03–51-23,968 and supported by the Uro Oncology Research Center of Tehran Medical Sciences University in the terms of sampling.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Mohammad Hossein Modarressi.

Electronic supplementary material

ESM 1

(XLS 36 kb)

ESM 2

(DOCX 17 kb)

ESM 3

(DOCX 23 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Afsharpad, M., Nowroozi, M.R., Mobasheri, M.B. et al. Cancer-Testis Antigens as New Candidate Diagnostic Biomarkers for Transitional Cell Carcinoma of Bladder. Pathol. Oncol. Res. 25, 191–199 (2019). https://doi.org/10.1007/s12253-017-0313-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12253-017-0313-4

Keywords

Navigation