Document Type : Short Paper
Authors
- Nadiah Abu
- Nurul Ainaa Adilah Rus Bakarurraini
- Siti Nurmi Nasir
- Muhiddin Ishak
- Rashidah Baharuddin
- Rahman Jamal
- Nurul Syakima Ab Mutalib
UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, 56000 Kuala Lumpur, Malaysia.
Abstract
Background: Cancer testis antigens (CTAs) are a class of immune-stimulating antigens often overexpressed in many types of cancers. The usage of the CTAs as immunotherapy targets have been widely investigated in different cancers including melanoma, hematological malignancies, and colorectal cancer. Studies have indicated that the epigenetic regulation of the CTAs such as the methylation status may affect the expression of the CTAs. However, the report on the methylation status of the CTAs is conflicting. The general methylation profile of the CTAs, especially in colorectal cancer, is still elusive.
Objective: To determine the methylation profile of the selected CTAs in our colorectal cancer patients.
Methods: A total of 54 pairs of colorectal cancer samples were subjected to DNA methylation profiling using the Infinium Human Methylation 450K bead chip.
Results: We found that most of the CTAs were hypomethylated, and CCNA1 and TMEM108 genes were among the few CTAs that were hypermethylated.
Conclusion: Overall, our brief report has managed to show the overall methylation profile in over the 200 CTAs in colorectal cancer and this could be used for further refining any immunotherapy targets.
Keywords
- Wagner, S., C.S. Mullins, and M. Linnebacher, Colorectal cancer vaccines: Tumor-associated antigens vs neoantigens. World J Gastroentero, 2018. 24(48): p. 5418-5432.
- Rus Bakarurraini, N.A.A. and N.S. Ab Mutalib, The Landscape of Tumor-Specific Antigens in Colorectal Cancer. Vaccines, 2020. 8(3): p. 371.
- van der Bruggen, P., et al., A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. Science, 1991. 254(5038): p. 1643.
- Krishnadas, D.K., F. Bai, and K.G. Lucas, Cancer testis antigen and immunotherapy. ImmunoTargets Ther, 2013. 2: p. 11-19.
- Salmaninejad, A., et al., Cancer/Testis Antigens: Expression, Regulation, Tumor Invasion, and Use in Immunotherapy of Cancers. Immunol Invest, 2016. 45(7): p. 619-40.
- Chi Soh, J.E., N. Abu, and R. Jamal, The potential immune-eliciting cancer testis antigens in colorectal cancer. Immunotherapy, 2018. 10(12): p. 1093-1104.
- Tarnowski, M., et al., Expression of Cancer Testis Antigens in Colorectal Cancer: New Prognostic and Therapeutic Implications. Dis Markers, 2016. 2016: p. 1987505.
- Soh, J.E., et al., Validation of immunogenic PASD1 peptides against HLA-A*24:02 colorectal cancer. Immunotherapy, 2019. 11(14): p. 1205-1219.
- De Smet, C., et al., DNA Methylation Is the Primary Silencing Mechanism for a Set of Germ Line- and Tumor-Specific Genes with a CpG-Rich Promoter. Mol Cell Biol, 1999. 19(11): p. 7327-7335.
- Zhang, W., et al., DNA hypomethylation-mediated activation of Cancer/Testis Antigen 45 (CT45) genes is associated with disease progression and reduced survival in epithelial ovarian cancer. Epigenetics, 2015. 10(8): p. 736-748.
- Serrano, A., et al., Methylated CpG points identified within MAGE-1 promoter are involved in gene repression. Int J Cancer, 1996. 68(4): p. 464-70.
- Odunsi, K., et al., Epigenetic potentiation of NY-ESO-1 vaccine therapy in human ovarian cancer. Cancer Immunol Res, 2014. 2(1): p. 37-49.
- Ishak, M., et al., Genome-Wide Open Chromatin Methylome Profiles in Colorectal Cancer. Biomolecules, 2020. 10(5): p. 719.
- Tian, Y., et al., ChAMP: updated methylation analysis pipeline for Illumina BeadChips. Bioinformatics, 2017. 33(24): p. 3982-3984.
- Dedeurwaerder, S., et al., Evaluation of the Infinium Methylation 450K technology. Epigenomics, 2011. 3(6): p. 771-84.
- Johnson, W.E., C. Li, and A. Rabinovic, Adjusting batch effects in microarray expression data using empirical Bayes methods. Biostatistics, 2006. 8(1): p. 118-127.
- Ritchie, M.E., et al., limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res, 2015. 43(7): p. 1-13.
- Barrett, T., et al., NCBI GEO: archive for functional genomics data sets—update. Nucleic Acids Res, 2012. 41(D1): p. 991-5.
- Díez-Villanueva, A., I. Mallona, and M.A. Peinado, Wanderer, an interactive viewer to explore DNA methylation and gene expression data in human cancer. Epigenet Chromatin, 2015. 8(1): p. 22.
- Charoentong, P., et al., Pan-cancer Immunogenomic Analyses Reveal Genotype-Immunophenotype Relationships and Predictors of Response to Checkpoint Blockade. Cell Rep, 2017. 18(1): p. 248-262.
- Chüeh, A.C., et al., Promoter hypomethylation of NY-ESO-1, association with clinicopathological features and PD-L1 expression in non-small cell lung cancer. Oncotarget, 2017. 8(43): p. 74036-74048.
- Colemon, A., T.M. Harris, and S. Ramanathan, DNA hypomethylation drives changes in MAGE-A gene expression resulting in alteration of proliferative status of cells. Genes Environ, 2020. 42(1): p. 24.
- Siebenkäs, C., et al., Inhibiting DNA methylation activates cancer testis antigens and expression of the antigen processing and presentation machinery in colon and ovarian cancer cells. PLoS One, 2017. 12(6): p. e0179501.
- Jakobsen, M.K., et al., The Cancer/Testis Antigen Gene VCX2 Is Rarely Expressed in Malignancies but Can Be Epigenetically Activated Using DNA Methyltransferase and Histone Deacetylase Inhibitors. Front Oncol, 2021. 10(3243).
- Song, X., et al., MicroRNA-874 Functions as a Tumor Suppressor by Targeting Cancer/Testis Antigen HCA587/MAGE-C2. J Cancer, 2016. 7(6): p. 656-663.
- Kutilin, D.S., [Regulation of Gene Expression of Cancer/Testis Antigens in Colorectal Cancer Patients]. Mol Biol (Mosk), 2020. 54(4): p. 580-595.
- Rettori, M.M., et al., TIMP3 and CCNA1 hypermethylation in HNSCC is associated with an increased incidence of second primary tumors. J Transl Med, 2013. 11(1): p. 316.
- Zuo, Q., et al., Methylation in the Promoters of HS3ST2 and CCNA1 Genes is Associated with Cervical Cancer in Uygur Women in Xinjiang. Int J Biol Marker, 2014. 29(4): p. 354-362.
- Yang, B., et al., Correlation of CCNA1 Promoter Methylation with Malignant Tumors: A Meta-Analysis Introduction. BioMed Res Int, 2015. 2015: p. 134027.
- Chang, L.-C., et al., Copy Number Alterations of Depressed Colorectal Neoplasm Predict the Survival and Response to Oxaliplatin in Proximal Colon Cancer. Cancers, 2020. 12(6): p. 1527.
- Yu, Z., et al., Transmembrane protein 108 involves in adult neurogenesis in the hippocampal dentate gyrus. Cell Biosci, 2019. 9(1): p. 9.
- Cheng, Y.-S., et al., MAEL promoter hypermethylation is associated with de-repression of LINE-1 in human hypospermatogenesis. Human Reproduction, 2017. 32(12): p. 2373-2381.
- Xiao, L., et al., Identification of a novel human cancer/testis gene MAEL that is regulated by DNA methylation. Molecular Biology Reports, 2010. 37(5): p. 2355-2360.
- Tang, Z., et al., GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res, 2017. 45(W1): p. 98-102.
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