Vol 74, No 5 (2024)
Research paper (original)
Published online: 2024-09-26
Expression of cancer testis genes in gastric neoplasms — a preliminary study
DOI: 10.5603/njo.99665
Nowotwory. Journal of Oncology 2024;74(5):289-299.
Abstract
Introduction. Scientists are currently searching for new and improved diagnostic markers and treatment modalities for gastric cancer. One putative target are the cancer/testis genes (CTGs), whose expression is restricted to male germ cells, trophoblasts and ovaries. CTGs are also aberrantly expressed in several types of cancers. In healthy somatic tissues, CTGs expression is either not detected or present at low levels. About 270 CTGs have been described thus far. The aim of this study was to investigate the expression levels of CTGs in stomach tissue samples from patients with gastric neoplasm, in relation to selected clinical and pathomorphological parameters.
Material and methods. 28 patients with histologically confirmed gastric neoplasms were included in this study. Total RNA was extracted from homogenates using the RNeasy Fibrous Tissue Mini Kit in accordance with the manufacturer’s protocol. A quantitative assessment of mRNA levels for 35 genes was performed using real-time RT-PCR.
Results. We report that 11 out of 35 CTGs tested (ATAD2, FBXO39, HORMAD1, IGSF11, IL13RA2, KIF2C, LDHC, OIP5, PLU1, SPAG9 and TTK) were significantly (p≤0.05) overexpressed in tumour tissue compared with healthy stomach samples isolated from the same patients. Additionally, our results indicated that overexpression of OIP5 was associated with gastric adenocarcinoma in women. Moreover, two of the tested CTGs (HORMAD1, TTK) were significantly overexpressed in tubular gastric adenocarcinoma. Additional analysis showed a correlation between KU-CT-1 expression in gastric adenocarcinoma and patient age at diagnosis.
Conclusions. Our results suggest that the overexpression of CTGs may be specific for gastric neoplasms, but it should be confirmed in larger numbers of patients.
Keywords: gastric neoplasmgenesbiomarkersCTGsexpression
References
- Ratajczak M, Tarnowski M, Borkowska S, et al. The Embryonic Rest Hypothesis of Cancer Development: 150 Years Later. Trends in Stem Cell Proliferation and Cancer Research. 2013: 51–63.
- Ross CA, Ross CA. The trophoblast model of cancer. Nutr Cancer. 2015; 67(1): 61–67.
- Jäger E, Knuth A. The discovery of cancer/testis antigens by autologous typing with T cell clones and the evolution of cancer vaccines. Cancer Immun. 2012; 12: 6.
- Ludwig Institute for Cancer Research. CT Antigens Database. http://www.cta.lncc.br (10.03.2024).
- Stevenson BJ, Iseli C, Panji S, et al. Rapid evolution of cancer/testis genes on the X chromosome. BMC Genomics. 2007; 8: 129.
- Dobrynin P, Matyunina E, Malov SV, et al. The novelty of human cancer/testis antigen encoding genes in evolution. Int J Genomics. 2013; 2013: 105108.
- Chen YT, Cao D, Chiu R, et al. Chromosome X-encoded Cancer/Testis antigens are less frequently expressed in non-seminomatous germ cell tumors than in seminomas. Cancer Immun. 2013; 13: 10.
- Gjerstorff MF, Andersen MH, Ditzel HJ. Oncogenic cancer/testis antigens: prime candidates for immunotherapy. Oncotarget. 2015; 6(18): 15772–15787.
- Peikert T, Specks U, Farver C, et al. Melanoma antigen A4 is expressed in non-small cell lung cancers and promotes apoptosis. Cancer Res. 2006; 66(9): 4693–4700.
- Fratta E, Coral S, Covre A, et al. The biology of cancer testis antigens: putative function, regulation and therapeutic potential. Mol Oncol. 2011; 5(2): 164–182.
- Caballero OL, Chen YT. Cancer/testis (CT) antigens: potential targets for immunotherapy. Cancer Sci. 2009; 100(11): 2014–2021.
- Almutairi MH, Alrubie TM, Almutairi BO, et al. The Expression Patterns of Human Cancer-Testis Genes Are Induced through Epigenetic Drugs in Colon Cancer Cells. Pharmaceuticals (Basel). 2022; 15(11).
- Zhang J, Zhang F, Zhang F, et al. Correlation between promoter methylation of the LDH-C4 gene and DNMT expression in breast cancer and their prognostic significance. Oncol Lett. 2022; 23(1): 35.
- Cheng YH, Wong EWp, Cheng CY. Cancer/testis (CT) antigens, carcinogenesis and spermatogenesis. Spermatogenesis. 2011; 1(3): 209–220.
- Li S, Meng Li, Zhu C, et al. The universal overexpression of a cancer testis antigen hiwi is associated with cancer angiogenesis. Oncol Rep. 2010; 23(4): 1063–1068.
- Carcas LP. Gastric cancer review. J Carcinog. 2014; 13: 14.
- Lochhead P, El-Omar EM. Gastric cancer. Br Med Bull. 2008; 85(1): 87–100.
- Janunger KG, Hafström L, Glimelius B. Chemotherapy in gastric cancer: a review and updated meta-analysis. Eur J Surg. 2002; 168(11): 597–608.
- Ahn CH, Kim YRi, Kim SS, et al. Mutational analysis of TTK gene in gastric and colorectal cancers with microsatellite instability. Cancer Res Treat. 2009; 41(4): 224–228.
- Chun HK, Chung KS, Kim HC, et al. OIP5 is a highly expressed potential therapeutic target for colorectal and gastric cancers. BMB Rep. 2010; 43(5): 349–354.
- Wang Z, Tang F, Qi G, et al. KDM5B is overexpressed in gastric cancer and is required for gastric cancer cell proliferation and metastasis. Am J Cancer Res. 2015; 5(1): 87–100.
- Miao ZF, Wang ZN, Zhao TT, et al. Overexpression of SPAG9 in human gastric cancer is correlated with poor prognosis. Virchows Arch. 2015; 467(5): 525–533.
- Nakamura Y, Tanaka F, Haraguchi N, et al. Clinicopathological and biological significance of mitotic centromere-associated kinesin overexpression in human gastric cancer. Br J Cancer. 2007; 97(4): 543–549.
- Zhang M-J, Zhang C-Z, Du W-J, et al. ATAD2 is overexpressed in gastric cancer and serves as an independent poor prognostic biomarker. Clin Transl Oncol. 2016; 18(8): 776–781.
- Yazarloo F, Shirkoohi R, Mobasheri MB, et al. Expression analysis of four testis-specific genes AURKC, OIP5, PIWIL2 and TAF7L in acute myeloid leukemia: a gender-dependent expression pattern. Med Oncol. 2013; 30(1): 368.
- Song MH, Ha JC, Lee SM, et al. Identification of BCP-20 (FBXO39) as a cancer/testis antigen from colon cancer patients by SEREX. Biochem Biophys Res Commun. 2011; 408(2): 195–201.
- Okada T, Akada M, Fujita T, et al. A novel cancer testis antigen that is frequently expressed in pancreatic, lung, and endometrial cancers. Clin Cancer Res. 2006; 12(1): 191–197.
- Jagadish N, Fatima R, Sharma A, et al. Sperm associated antigen 9 (SPAG9) a promising therapeutic target of ovarian carcinoma. Tumour Biol. 2018; 40(5): 1010428318773652.
- Tavakoli Koudehi A, Mahjoubi B, Mirzaei R, et al. AKAP4, SPAG9 and NY-ESO-1 in Iranian Colorectal Cancer Patients as Probable Diagnostic and Prognostic Biomarkers. Asian Pac J Cancer Prev. 2018; 19(2): 463–469.
- Nair M, Sandhu SS, Sharma AK. Cancer molecular markers: A guide to cancer detection and management. Semin Cancer Biol. 2018; 52(Pt 1): 39–55.
- Tarnowski M, Czerewaty M, Deskur A, et al. Expression of Cancer Testis Antigens in Colorectal Cancer: New Prognostic and Therapeutic Implications. Dis Markers. 2016; 2016: 1987505.
- Mori Y, Sato F, Selaru FM, et al. Instabilotyping reveals unique mutational spectra in microsatellite-unstable gastric cancers. Cancer Res. 2002; 62(13): 3641–3645.
- Menyhárt O, Pongor LS, Győrffy B. Mutations Defining Patient Cohorts With Elevated PD-L1 Expression in Gastric Cancer. Front Pharmacol. 2018; 9: 1522.
- Mills GB, Schmandt R, McGill M, et al. Expression of TTK, a novel human protein kinase, is associated with cell proliferation. J Biol Chem. 1992; 267(22): 16000–16006.
- Wang D, Zhu H, Guo M, et al. Expression and prognostic value of cell-cycle-associated genes in gastric adenocarcinoma. BMC Gastroenterol. 2018; 18(1): 81.
- Lee HH, Song KY, Park CH, et al. Undifferentiated-type gastric adenocarcinoma: prognostic impact of three histological types. World J Surg Oncol. 2012; 10: 254.
- Aung PP, Oue N, Mitani Y, et al. Systematic search for gastric cancer-specific genes based on SAGE data: melanoma inhibitory activity and matrix metalloproteinase-10 are novel prognostic factors in patients with gastric cancer. Oncogene. 2006; 25(17): 2546–2557.
- Nakamura Y, Tanaka F, Nagahara H, et al. Opa interacting protein 5 (OIP5) is a novel cancer-testis specific gene in gastric cancer. Ann Surg Oncol. 2007; 14(2): 885–892.
- Zheng J, You W, Zheng C, et al. Knockdown of FBXO39 inhibits proliferation and promotes apoptosis of human osteosarcoma U-2OS cells. Oncol Lett. 2018; 16(2): 1849–1854.
- Yang Y, Zhao Y, Sun G, et al. FBXO39 predicts poor prognosis and correlates with tumor progression in cervical squamous cell carcinoma. Pathol Res Pract. 2022; 238: 154090.
- Koslowski M, Türeci O, Bell C, et al. Multiple splice variants of lactate dehydrogenase C selectively expressed in human cancer. Cancer Res. 2002; 62(22): 6750–6755.
- Xie H, Xue YQ, Liu P, et al. Multi-parameter gene expression profiling of peripheral blood for early detection of hepatocellular carcinoma. World J Gastroenterol. 2018; 24(3): 371–378.
- Ren B, Wei X, Zou G, et al. Cancer testis antigen SPAG9 is a promising marker for the diagnosis and treatment of lung cancer. Oncol Rep. 2016; 35(5): 2599–2605.
- Guinn BA, Bland EA, Lodi U, et al. Humoral detection of leukaemia-associated antigens in presentation acute myeloid leukaemia. Biochem Biophys Res Commun. 2005; 335(4): 1293–1304.
- Kanojia D, Garg M, Gupta S, et al. Sperm-associated antigen 9, a novel biomarker for early detection of breast cancer. Cancer Epidemiol Biomarkers Prev. 2009; 18(2): 630–639.
- Garg M, Kanojia D, Salhan S, et al. Sperm-associated antigen 9 is a biomarker for early cervical carcinoma. Cancer. 2009; 115(12): 2671–2683.
- Lin C, Liu H, Zhang H, et al. Interleukin-13 receptor α2 is associated with poor prognosis in patients with gastric cancer after gastrectomy. Oncotarget. 2016; 7(31): 49281–49288.
- Jarboe JS, Johnson KR, Choi Y, et al. Expression of interleukin-13 receptor alpha2 in glioblastoma multiforme: implications for targeted therapies. Cancer Res. 2007; 67(17): 7983–7986.
- Barderas R, Bartolomé RA, Fernandez-Aceñero MJ, et al. High expression of IL-13 receptor α2 in colorectal cancer is associated with invasion, liver metastasis, and poor prognosis. Cancer Res. 2012; 72(11): 2780–2790.
- Fujisawa T, Joshi B, Nakajima A, et al. A novel role of interleukin-13 receptor alpha2 in pancreatic cancer invasion and metastasis. Cancer Res. 2009; 69(22): 8678–8685.
- Wanibuchi M, Kataoka-Sasaki Y, Sasaki M, et al. Interleukin-13 receptor alpha 2 as a marker of poorer prognosis in high-grade astrocytomas. J Neurosurg Sci. 2018; 62(3): 239–244.
- Watanabe T, Suda T, Tsunoda T, et al. Identification of immunoglobulin superfamily 11 (IGSF11) as a novel target for cancer immunotherapy of gastrointestinal and hepatocellular carcinomas. Cancer Sci. 2005; 96(8): 498–506.
- Katoh M, Katoh M. IGSF11 gene, frequently up-regulated in intestinal-type gastric cancer, encodes adhesion molecule homologous to CXADR, FLJ22415 and ESAM. Int J Oncol. 2003; 23(2): 525–531.
- Zheng Le, Li T, Zhang Yi, et al. Oncogene ATAD2 promotes cell proliferation, invasion and migration in cervical cancer. Oncol Rep. 2015; 33(5): 2337–2344.
- Ciró M, Prosperini E, Quarto M, et al. ATAD2 is a novel cofactor for MYC, overexpressed and amplified in aggressive tumors. Cancer Res. 2009; 69(21): 8491–8498.
- Murakami H, Ito S, Tanaka H, et al. Establishment of new intraperitoneal paclitaxel-resistant gastric cancer cell lines and comprehensive gene expression analysis. Anticancer Res. 2013; 33(10): 4299–4307.