Reduction of T-box 15 gene expression in tumor tissue is a prognostic biomarker for patients with hepatocellular carcinoma

Yuji Morine, Tohru Utsunomiya, Yu Saito, Shinichiro Yamada, Satoru Imura, Tetsuya Ikemoto, Akihiro Kitagawa, Yuta Kobayashi, Seiichiro Takao, Keisuke Kosai, Koshi Mimori, Yasuhito Tanaka, Mitsuo Shimada

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)4803-4812
Number of pages10
JournalOncotarget
Volume11
Issue number35
DOIs
Publication statusPublished - 2021
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology

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