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ID 116613
Author
Kitagawa, Akihiro Kyushu University
Kobayashi, Yuta Kyushu University
Takao, Seiichiro Kyushu University
Kosai, Keisuke Kyushu University
Mimori, Koshi Kyushu University
Tanaka, Yasuhito Kumamoto University
Keywords
genome-wide analysis
methylation
tumor suppressor gene
prognostic biomarker
hepatocellular carcinoma
Content Type
Journal Article
Description
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.
Journal Title
Oncotarget
ISSN
19492553
Publisher
Impact Journals
Volume
11
Issue
52
Start Page
4803
End Page
4812
Published Date
2020-12-29
Rights
This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0) (https://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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DOI (Published Version)
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language
eng
TextVersion
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departments
Medical Sciences
University Hospital