DNA hypomethylation-mediated activation ofCancer/Testis Antigen 45(CT45) genes is associated with disease progression and reduced survival in epithelial ovarian cancer
| العنوان: | DNA hypomethylation-mediated activation ofCancer/Testis Antigen 45(CT45) genes is associated with disease progression and reduced survival in epithelial ovarian cancer |
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| المؤلفون: | Petra A. Link, Austin Miller, Carter J. Barger, Wa Zhang, S.N. Akers, Paulette Mhawech-Fauceglia, Adam R. Karpf, Kunle Odunsi |
| المصدر: | Epigenetics |
| بيانات النشر: | Informa UK Limited, 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | epithelial ovarian cancer, Cancer Research, endocrine system diseases, Azacitidine, Decitabine, cancer testis antigen genes, CT45, cancer germline genes, Carcinoma, Ovarian Epithelial, Biology, Epigenesis, Genetic, Antigens, Neoplasm, Cell Line, Tumor, medicine, Humans, Neoplasms, Glandular and Epithelial, RNA, Messenger, Epigenetics, Promoter Regions, Genetic, Molecular Biology, Aged, Ovarian Neoplasms, DNA methylation, Cancer, Promoter, Middle Aged, medicine.disease, female genital diseases and pregnancy complications, 3. Good health, Gene Expression Regulation, Neoplastic, tumor antigens, Disease Progression, Cancer research, Cancer/testis antigens, Female, Research Paper, DNA hypomethylation, medicine.drug |
| الوصف: | Epithelial ovarian cancer (EOC) is a highly lethal malignancy due to a lack of early detection approaches coupled with poor outcomes for patients with clinically advanced disease. Cancer-testis (CT) or cancer-germline genes encode antigens known to generate spontaneous anti-tumor immunity in cancer patients. CT45 genes are a recently discovered 6-member family of X-linked CT genes with oncogenic function. Here, we determined CT45 expression in EOC and fully defined its epigenetic regulation by DNA methylation. CT45 was silent and hypermethylated in normal control tissues, but a large subset of EOC samples showed increased CT45 expression in conjunction with promoter DNA hypomethylation. In contrast, copy number status did not correlate with CT45 expression in the TCGA database for EOC. CT45 promoter methylation inversely correlated with both CT45 mRNA and protein expression, the latter determined using IHC staining of an EOC TMA. CT45 expression was increased and CT45 promoter methylation was decreased in late-stage and high-grade EOC, and both measures were associated with poor survival. CT45 hypomethylation was directly associated with LINE-1 hypomethylation, and CT45 was frequently co-expressed with other CT antigen genes in EOC. Decitabine treatment induced CT45 mRNA and protein expression in EOC cells, and promoter transgene analyses indicated that DNA methylation directly represses CT45 promoter activity. These data verify CT45 expression and promoter hypomethylation as possible prognostic biomarkers, and suggest CT45 as an immunological or therapeutic target in EOC. Treatment with decitabine or other epigenetic modulators could provide a means for more effective immunological targeting of CT45. |
| تدمد: | 1559-2308 1559-2294 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9f141bf4ce9b5d72a57131836d004a91 https://doi.org/10.1080/15592294.2015.1062206 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....9f141bf4ce9b5d72a57131836d004a91 |
| قاعدة البيانات: | OpenAIRE |
PDF full text from Publisher | تدمد: | 15592308 15592294 |
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