Top

Published in:

01-01-2019 | Original Article

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

Authors: Mandana Afsharpad, Mohammad Reza Nowroozi, Maryam Beigom Mobasheri, Mohsen Ayati, Leila Nekoohesh, Mojtaba Saffari, Kazem Zendehdel, Mohammad Hossein Modarressi

Published in: Pathology & Oncology Research | Issue 1/2019

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.

Available only for authorised users

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

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–e47CrossRefPubMed

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 CrossRef

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

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 CrossRefPubMed

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 CrossRefPubMed

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 CrossRefPubMed

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):485–492CrossRefPubMed

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

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 CrossRefPubMed

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 CrossRefPubMed

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 CrossRefPubMed

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):398–407CrossRefPubMedPubMedCentral

14.

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

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 CrossRefPubMed

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):1365–1371CrossRefPubMed

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 CrossRefPubMedPubMedCentral

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 CrossRefPubMed

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 CrossRefPubMed

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 CrossRefPubMed

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 CrossRefPubMedPubMedCentral

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

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):60–64CrossRefPubMed

24.

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

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):8326–8336CrossRefPubMedPubMedCentral

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):233–244CrossRefPubMed

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):9954–9962CrossRefPubMed

Title: Cancer-Testis Antigens as New Candidate Diagnostic Biomarkers for Transitional Cell Carcinoma of Bladder
Authors: Mandana Afsharpad
Mohammad Reza Nowroozi
Maryam Beigom Mobasheri
Mohsen Ayati
Leila Nekoohesh
Mojtaba Saffari
Kazem Zendehdel
Mohammad Hossein Modarressi
Publication date: 01-01-2019
Publisher: Springer Netherlands
Published in: Pathology & Oncology Research / Issue 1/2019
Print ISSN: 1219-4956
Electronic ISSN: 1532-2807
DOI: https://doi.org/10.1007/s12253-017-0313-4

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2019

Suppression of Angiotensin-(1–7) on the Disruption of Blood-Brain Barrier in Rat of Brain Glioma

Advantages of 18F FDG-PET/CT over Conventional Staging for Sarcoma Patients

The Impact of Peritumoral Retraction Clefting & Intratumoral Eosinophils on Overall Survival in Oral Squamous Carcinoma Patients

Overexpression of TIMP-1 and Sensitivity to Topoisomerase Inhibitors in Glioblastoma Cell Lines

Invitro Evaluation of Torin2 and 2, 6-Dihydroxyacetophenone in Colorectal Cancer Therapy

Clinical Implications of NRAS Overexpression in Resectable Pancreatic Adenocarcinoma Patients

Keynote webinar | Spotlight on antibody–drug conjugates in cancer