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. 2020 Dec 29;11(52):4803-4812.
doi: 10.18632/oncotarget.27852.

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

Yuji Morine  1 , Tohru Utsunomiya  1 , Yu Saito  1 , Shinichiro Yamada  1 , Satoru Imura  1 , Tetsuya Ikemoto  1 , Akihiro Kitagawa  2 , Yuta Kobayashi  2 , Seiichiro Takao  2 , Keisuke Kosai  2 , Koshi Mimori  2 , Yasuhito Tanaka  3 , Mitsuo Shimada  1
Affiliations

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

Yuji Morine et al. Oncotarget. .

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.

Keywords: genome-wide analysis; hepatocellular carcinoma; methylation; prognostic biomarker; tumor suppressor gene.

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Conflict of interest statement

CONFLICTS OF INTEREST Authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1. Volcano plots of DNA methylation in tumor tissues compared with nontumor tissue.
Significant associations are indicated in red.
Figure 2
Figure 2
(A) TBX15 mRNA expression in tumor tissues and nontumor tissues. (B) TBX15 protein expression in tumor tissues and nontumor tissues.
Figure 3
Figure 3
(A) Overall survival as a function of TBX15 mRNA expression. (B) Disease-free survival as a function of TBX15 mRNA expression.
See this image and copyright information in PMC

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