Reduction of T-Box 15 gene expression in tumor tissue is a prognostic biomarker for patients with hepatocellular carcinoma
Autor: | Yasuhito Tanaka, Tetsuya Ikemoto, Shinichiro Yamada, Yuji Morine, Mitsuo Shimada, Yuta Kobayashi, Satoru Imura, Akihiro Kitagawa, Seiichiro Takao, Yu Saito, Koshi Mimori, Tohru Utsunomiya, Keisuke Kosai |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Tumor suppressor gene medicine.disease_cause 03 medical and health sciences 0302 clinical medicine Gene expression medicine tumor suppressor gene prognostic biomarker Gene business.industry hepatocellular carcinoma Methylation medicine.disease 030104 developmental biology Oncology Tumor progression 030220 oncology & carcinogenesis Hepatocellular carcinoma DNA methylation Cancer research methylation Carcinogenesis business Research Paper genome-wide analysis |
Zdroj: | Oncotarget |
ISSN: | 1949-2553 |
DOI: | 10.18632/oncotarget.27852 |
Popis: | Genome-wide analysis is widely applied to detect molecular alterations during oncogenesis and tumor progression. We analyzed DNA methylation profiles of hepatocellular carcinoma (HCC), and investigated the clinical role of most heypermethylated of tumor, encodes T-box 15 (TBX15), which was originally involved in mesodermal differentiation. We conducted a genome-wide analysis of DNA methylation of tumor and non-tumor tissue of 15 patients with HCC, and revealed TBX15 was the most hypermethylated gene of tumor (Beta-value in tumor tissue = 0.52 compared with non-tumor tissue). Another validation set, which comprised 58 HCC with radical resection, was analyzed to investigate the relationships between tumor phenotype and TBX15 mRNA expression. TBX15 mRNA levels in tumor tissues were significantly lower compared with those of nontumor tissues (p < 0.0001). When we assigned a cutoff value = 0.5-fold, the overall survival 5-year survival rates of the low-expression group (n = 17) were significantly shorter compared with those of the high-expression group (n = 41) (43.3% vs. 86.2%, p = 0.001). Multivariate analysis identified low TBX15 expression as an independent prognostic factor for overall and disease-free survival. Therefore, genome-wide DNA methylation profiling indicates that hypermethylation and reduced expression of TBX15 in tumor tissue represents a potential biomarker for predicting poor survival of patients with HCC. |
Databáze: | OpenAIRE |
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