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Identifying Apoptosis-Related Transcriptomic Aberrations and Revealing Clinical Relevance as Diagnostic and Prognostic Biomarker in Hepatocellular Carcinoma

In view of the unsatisfactory treatment outcome of liver cancer under current treatment, where the mortality rate is high and the survival rate is poor, in this study we aimed to use RNA sequencing data to explore potential molecular markers that can be more effective in predicting diagnosis and pro...

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Autores principales: Zhu, Jinyu, Tang, Bufu, Lv, Xiuling, Meng, Miaomiao, Weng, Qiaoyou, Zhang, Nannan, Li, Jie, Fan, Kai, Zheng, Liyun, Fang, Shiji, Xu, Min, Ji, Jiansong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931692/
https://www.ncbi.nlm.nih.gov/pubmed/33680905
http://dx.doi.org/10.3389/fonc.2020.519180
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author Zhu, Jinyu
Tang, Bufu
Lv, Xiuling
Meng, Miaomiao
Weng, Qiaoyou
Zhang, Nannan
Li, Jie
Fan, Kai
Zheng, Liyun
Fang, Shiji
Xu, Min
Ji, Jiansong
author_facet Zhu, Jinyu
Tang, Bufu
Lv, Xiuling
Meng, Miaomiao
Weng, Qiaoyou
Zhang, Nannan
Li, Jie
Fan, Kai
Zheng, Liyun
Fang, Shiji
Xu, Min
Ji, Jiansong
author_sort Zhu, Jinyu
collection PubMed
description In view of the unsatisfactory treatment outcome of liver cancer under current treatment, where the mortality rate is high and the survival rate is poor, in this study we aimed to use RNA sequencing data to explore potential molecular markers that can be more effective in predicting diagnosis and prognosis of hepatocellular carcinoma. RNA sequencing data and corresponding clinical information were obtained from multiple databases. After matching with the apoptotic genes from the Deathbase database, 14 differentially expressed human apoptosis genes were obtained. Using univariate and multivariate Cox regression analyses, two apoptosis genes (BAK1 and CSE1L) were determined to be closely associated with overall survival (OS) in HCC patients. And subsequently experiments also validated that knockdown of BAK1 and CSE1L significantly inhibited cell proliferation and promoted apoptosis in the HCC. Then the two genes were used to construct a prognostic signature and diagnostic models. The high-risk group showed lower OS time compared to low-risk group in the TCGA cohort (P < 0.001, HR = 2.11), GSE14520 cohort (P = 0.003, HR = 1.85), and ICGC cohort (P < 0.001, HR = 4). And the advanced HCC patients showed higher risk score and worse prognosis compared to early-stage HCC patients. Moreover, the prognostic signature was validated to be an independent prognostic factor. The diagnostic models accurately predicted HCC from normal tissues and dysplastic nodules in the training and validation cohort. These results indicated that the two apoptosis-related signature effectively predicted diagnosis and prognosis of HCC and may serve as a potential biomarker and therapeutic target for HCC.
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spelling pubmed-79316922021-03-05 Identifying Apoptosis-Related Transcriptomic Aberrations and Revealing Clinical Relevance as Diagnostic and Prognostic Biomarker in Hepatocellular Carcinoma Zhu, Jinyu Tang, Bufu Lv, Xiuling Meng, Miaomiao Weng, Qiaoyou Zhang, Nannan Li, Jie Fan, Kai Zheng, Liyun Fang, Shiji Xu, Min Ji, Jiansong Front Oncol Oncology In view of the unsatisfactory treatment outcome of liver cancer under current treatment, where the mortality rate is high and the survival rate is poor, in this study we aimed to use RNA sequencing data to explore potential molecular markers that can be more effective in predicting diagnosis and prognosis of hepatocellular carcinoma. RNA sequencing data and corresponding clinical information were obtained from multiple databases. After matching with the apoptotic genes from the Deathbase database, 14 differentially expressed human apoptosis genes were obtained. Using univariate and multivariate Cox regression analyses, two apoptosis genes (BAK1 and CSE1L) were determined to be closely associated with overall survival (OS) in HCC patients. And subsequently experiments also validated that knockdown of BAK1 and CSE1L significantly inhibited cell proliferation and promoted apoptosis in the HCC. Then the two genes were used to construct a prognostic signature and diagnostic models. The high-risk group showed lower OS time compared to low-risk group in the TCGA cohort (P < 0.001, HR = 2.11), GSE14520 cohort (P = 0.003, HR = 1.85), and ICGC cohort (P < 0.001, HR = 4). And the advanced HCC patients showed higher risk score and worse prognosis compared to early-stage HCC patients. Moreover, the prognostic signature was validated to be an independent prognostic factor. The diagnostic models accurately predicted HCC from normal tissues and dysplastic nodules in the training and validation cohort. These results indicated that the two apoptosis-related signature effectively predicted diagnosis and prognosis of HCC and may serve as a potential biomarker and therapeutic target for HCC. Frontiers Media S.A. 2021-02-18 /pmc/articles/PMC7931692/ /pubmed/33680905 http://dx.doi.org/10.3389/fonc.2020.519180 Text en Copyright © 2021 Zhu, Tang, Lv, Meng, Weng, Zhang, Li, Fan, Zheng, Fang, Xu and Ji http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Zhu, Jinyu
Tang, Bufu
Lv, Xiuling
Meng, Miaomiao
Weng, Qiaoyou
Zhang, Nannan
Li, Jie
Fan, Kai
Zheng, Liyun
Fang, Shiji
Xu, Min
Ji, Jiansong
Identifying Apoptosis-Related Transcriptomic Aberrations and Revealing Clinical Relevance as Diagnostic and Prognostic Biomarker in Hepatocellular Carcinoma
title Identifying Apoptosis-Related Transcriptomic Aberrations and Revealing Clinical Relevance as Diagnostic and Prognostic Biomarker in Hepatocellular Carcinoma
title_full Identifying Apoptosis-Related Transcriptomic Aberrations and Revealing Clinical Relevance as Diagnostic and Prognostic Biomarker in Hepatocellular Carcinoma
title_fullStr Identifying Apoptosis-Related Transcriptomic Aberrations and Revealing Clinical Relevance as Diagnostic and Prognostic Biomarker in Hepatocellular Carcinoma
title_full_unstemmed Identifying Apoptosis-Related Transcriptomic Aberrations and Revealing Clinical Relevance as Diagnostic and Prognostic Biomarker in Hepatocellular Carcinoma
title_short Identifying Apoptosis-Related Transcriptomic Aberrations and Revealing Clinical Relevance as Diagnostic and Prognostic Biomarker in Hepatocellular Carcinoma
title_sort identifying apoptosis-related transcriptomic aberrations and revealing clinical relevance as diagnostic and prognostic biomarker in hepatocellular carcinoma
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931692/
https://www.ncbi.nlm.nih.gov/pubmed/33680905
http://dx.doi.org/10.3389/fonc.2020.519180
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