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

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 originall...

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Autores principales: Morine, Yuji, Utsunomiya, Tohru, Saito, Yu, Yamada, Shinichiro, Imura, Satoru, Ikemoto, Tetsuya, Kitagawa, Akihiro, Kobayashi, Yuta, Takao, Seiichiro, Kosai, Keisuke, Mimori, Koshi, Tanaka, Yasuhito, Shimada, Mitsuo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779253/
https://www.ncbi.nlm.nih.gov/pubmed/33447348
http://dx.doi.org/10.18632/oncotarget.27852
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author Morine, Yuji
Utsunomiya, Tohru
Saito, Yu
Yamada, Shinichiro
Imura, Satoru
Ikemoto, Tetsuya
Kitagawa, Akihiro
Kobayashi, Yuta
Takao, Seiichiro
Kosai, Keisuke
Mimori, Koshi
Tanaka, Yasuhito
Shimada, Mitsuo
author_facet Morine, Yuji
Utsunomiya, Tohru
Saito, Yu
Yamada, Shinichiro
Imura, Satoru
Ikemoto, Tetsuya
Kitagawa, Akihiro
Kobayashi, Yuta
Takao, Seiichiro
Kosai, Keisuke
Mimori, Koshi
Tanaka, Yasuhito
Shimada, Mitsuo
author_sort Morine, Yuji
collection PubMed
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.
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spelling pubmed-77792532021-01-13 Reduction of T-Box 15 gene expression in tumor tissue is a prognostic biomarker for patients with hepatocellular carcinoma Morine, Yuji Utsunomiya, Tohru Saito, Yu Yamada, Shinichiro Imura, Satoru Ikemoto, Tetsuya Kitagawa, Akihiro Kobayashi, Yuta Takao, Seiichiro Kosai, Keisuke Mimori, Koshi Tanaka, Yasuhito Shimada, Mitsuo Oncotarget Research Paper 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. Impact Journals LLC 2020-12-29 /pmc/articles/PMC7779253/ /pubmed/33447348 http://dx.doi.org/10.18632/oncotarget.27852 Text en Copyright: © 2020 Morine et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Morine, Yuji
Utsunomiya, Tohru
Saito, Yu
Yamada, Shinichiro
Imura, Satoru
Ikemoto, Tetsuya
Kitagawa, Akihiro
Kobayashi, Yuta
Takao, Seiichiro
Kosai, Keisuke
Mimori, Koshi
Tanaka, Yasuhito
Shimada, Mitsuo
Reduction of T-Box 15 gene expression in tumor tissue is a prognostic biomarker for patients with hepatocellular carcinoma
title Reduction of T-Box 15 gene expression in tumor tissue is a prognostic biomarker for patients with hepatocellular carcinoma
title_full Reduction of T-Box 15 gene expression in tumor tissue is a prognostic biomarker for patients with hepatocellular carcinoma
title_fullStr Reduction of T-Box 15 gene expression in tumor tissue is a prognostic biomarker for patients with hepatocellular carcinoma
title_full_unstemmed Reduction of T-Box 15 gene expression in tumor tissue is a prognostic biomarker for patients with hepatocellular carcinoma
title_short Reduction of T-Box 15 gene expression in tumor tissue is a prognostic biomarker for patients with hepatocellular carcinoma
title_sort reduction of t-box 15 gene expression in tumor tissue is a prognostic biomarker for patients with hepatocellular carcinoma
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779253/
https://www.ncbi.nlm.nih.gov/pubmed/33447348
http://dx.doi.org/10.18632/oncotarget.27852
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