Relationship between the transcriptional activity of СT-genes and survival in colorectal cancer patients
https://doi.org/10.21294/1814-4861-2022-21-1-37-46
Abstract
Introduction. High incidence and mortality rates of colorectal cancer indicate an urgent need for the use of new highly specific diagnostic and prognostic molecular markers. In this aspect, cancer testis antigens (CTA s) are of particular interest.
The aim of the study was to analyze the relationship between the transcriptional activity of CTA s and survival in colorectal cancer patients with metastases (T1–4N1–2M1–2) and without metastases (T1–3N0M0).
Results. The relative expression of 16 genetic loci (MAGE-A1, MAGE-A2, MAGE-A3, MAGE-A4, MAGE-B1, MAGE-B2, GAGE-1, GAGE-3, GAGE-4, MAGE-C1, BAGE, XAGE3, NYESO1, SSX2, SCP1 and PRAME1) was determined by real-time PC R. In colorectal cancer patients having no metastases, the expression of SSX2 and PRAME1 genes was significantly higher and the expression of BAGE was significantly lower in colon tumor tissue than in normal tissue (p<0.05). In colorectal cancer patient with metastases, the expression of GAGE1, SCP1 and PRAME1 genes was significantly higher and the expression of MAGEA2, MAGEB1, MAGEB2, GAGE4 and NY-ESO1 genes was significantly lower in colon tumor tissue than in normal tissue (p<0.05). The expression of the GAGE1, BAGE, SSX2, MAGEA2, SCP1 and MAGEB1 genes was found to have a significant impact on the overall survival and the development of distant metastasis (p<0.05).
Conclusion. The data obtained are the basis for the formation of a panel of effective immunotherapeutic targets and prognostic markers for colorectal cancer patients with and without metastases.
About the Authors
D. S. KutilinRussian Federation
Denis S. Kutilin, PhD, Senior Researcher, Laboratory of Molecular Oncology
SPIN-code: 8382-4460
63, 14th Line Street, Rostov-on-Don, 344037, Russia
O. I. Kit
Russian Federation
Oleg I. Kit, MD, Professor, Corresponding Member of the Russian Academy of Sciences, Director
SPIN-code: 1728-0329. Researcher ID (WOS): U-2241-2017. Author ID (Scopus): 55994103100
63, 14th Line Street, Rostov-on-Don, 344037, Russia
References
1. Kutilin D.S., Kosheleva N.G., Gusareva M.A., Kharagezov D.A., Dontsov V.A., Poluektov S.I., Zema T.V., Liman N.A., Shlyakhova O.V., Udalenkova I.A. The effect of transcriptional activity of genes that regulate DNA repair on the effectiveness of radiation therapy of rectal tumors. Modern Problems of Science and Education. 2019; 6: 142. (in Russian)
2. Soldatova K.I., Kolesnikov E.N., Gabrichidze P.N. Transcriptional activity features of cancer-testis antigens in patients with metastatic and nonmetastatic colorectal cancer. Modern Problems of Science and Education. 2018; 5: 108. (in Russian)
3. Kit O.I., Soldatova K.I., Kutilin D.S., Vodolazhsky D.I Cancer-testis antigens in colon tumors diagnostics. Modern Problems of Science and Education. 2018; 2: 10. (in Russian)
4. Chi Soh J.E., Abu N., Jamal R. The potential immune-eliciting cancer testis antigens in colorectal cancer. Immunotherapy. 2018 Sep; 10(12): 1093–1104. doi: 10.2217/imt-2018-0044.
5. Golyshko P.V., Novikov D.V., Ananev S.V., Baryshnikov K.A., Novikov V.V. A Search for cancer-testis genes expression in blood and biopsy of patients with colorectal cancer. Russian Journal of Biotherapy. 2015; 14(1): 19–24. (in Russian)
6. Sammut J., Wakeman J.A., Stuart N., McFarlane R.J. Cancer/ Testis Antigens and Colorectal Cancer. J Genet Syndr Gene Ther. 2013; 4: 149.
7. Kutilin D.S., Nikitin I.S., Kit O.I. Features of some transcription factors gene expression in the malignancy tissues of the corpus uteri. Advances in Molecular Oncology. 2019; 6(1): 57–62. (in Russian)
8. Vodolazhsky D.I., Kutilin D.S., Soldatova K.I. Study of the stability of expression of reference genetic loci during malignancy of colon tissues. 5 itogovaya nauchnaya sessiya molodykh uchonykh. RostGMU. 2018: 33–34. (in Russian)
9. Vodolazhskiy D.I., Kutilin D.S., Mogushkova Kh.A., Kit O.I. Transcriptional profile of cancer-testicular antigens in patients with breast cancer. Medical Immunology. 2018; 20(3): 383–90. (in Russian)
10. Kutilin D.S., Dimitriadi S.N., Vodolazhsky D.I., Frantsiyants H.M., Kit O.I. Effect of thermal ischemia-reperfusion on expression of apoptosis-regulating genes in the renal tissue of patients with renal cell carcinoma. Nephrology. 2017; 21(1): 80–6. (in Russian)
11. Shantha Kumara H.M., Grieco M.J., Caballero O.L., Su T., Ahmed A., Ritter E., Gnjatic S., Cekic V., Old L.J., Simpson A.J., Cordon- Cardo C., Whelan R.L. MAGE-A3 is highly expressed in a subset of colorectal cancer patients. Cancer Immun. 2012; 12: 16.
12. Li M., Yuan Y.H., Han Y., Liu Y.X., Yan L., Wang Y., Gu J. Expression profile of cancer-testis genes in 121 human colorectal cancer tissue and adjacent normal tissue. Clin Cancer Res. 2005 Mar 1; 11(5): 1809–14. doi: 10.1158/1078-0432.CCR-04-1365.
13. Wei X., Chen F., Xin K., Wang Q., Yu L., Liu B., Liu Q. Cancer- Testis Antigen Peptide Vaccine for Cancer Immunotherapy: Progress and Prospects. Transl Oncol. 2019 May; 12(5): 733–8. doi: 10.1016/j.tranon.2019.02.008.
14. Salmaninejad A., Zamani M.R., Pourvahedi M., Golchehre Z., Hosseini Bereshneh A., Rezaei N. Cancer/Testis Antigens: Expression, Regulation, Tumor Invasion, and Use in Immunotherapy of Cancers. Immunol Invest. 2016 Oct; 45(7): 619–40. doi: 10.1080/08820139.2016.1197241.
Review
For citations:
Kutilin D.S., Kit O.I. Relationship between the transcriptional activity of СT-genes and survival in colorectal cancer patients. Siberian journal of oncology. 2022;21(1):37-46. (In Russ.) https://doi.org/10.21294/1814-4861-2022-21-1-37-46