Screening and Identification of Potential Biomarkers in Hepatitis B Virus-Related Hepatocellular Carcinoma by Bioinformatics Analysis
Hepatocellular carcinoma (HCC) is one of the most lethal cancers globally. Hepatitis B virus (HBV) infection might cause chronic hepatitis and cirrhosis, leading to HCC. To screen prognostic genes and therapeutic targets for HCC by bioinformatics analysis and determine the mechanisms underlying HBV-...
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doaj-68d14c4285ca4fa6bde4b8cc266954282020-11-25T03:27:42ZengFrontiers Media S.A.Frontiers in Genetics1664-80212020-09-011110.3389/fgene.2020.555537555537Screening and Identification of Potential Biomarkers in Hepatitis B Virus-Related Hepatocellular Carcinoma by Bioinformatics AnalysisXian-Chang Zeng0Lu Zhang1Wen-Jun Liao2Lu Ao3Ze-Man Lin4Wen Kang5Wan-Nan Chen6Wan-Nan Chen7Xu Lin8Xu Lin9Key Laboratory of Gastrointestinal Cancer, Ministry of Education, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, ChinaKey Laboratory of Gastrointestinal Cancer, Ministry of Education, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, ChinaKey Laboratory of Gastrointestinal Cancer, Ministry of Education, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, ChinaFujian Key Laboratory of Medical Bioinformatics, Department of Bioinformatics, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, ChinaFujian Key Laboratory of Medical Bioinformatics, Department of Bioinformatics, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, ChinaKey Laboratory of Gastrointestinal Cancer, Ministry of Education, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, ChinaKey Laboratory of Gastrointestinal Cancer, Ministry of Education, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, ChinaFujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University, Fuzhou, ChinaKey Laboratory of Gastrointestinal Cancer, Ministry of Education, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, ChinaFujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University, Fuzhou, ChinaHepatocellular carcinoma (HCC) is one of the most lethal cancers globally. Hepatitis B virus (HBV) infection might cause chronic hepatitis and cirrhosis, leading to HCC. To screen prognostic genes and therapeutic targets for HCC by bioinformatics analysis and determine the mechanisms underlying HBV-related HCC, three high-throughput RNA-seq based raw datasets, namely GSE25599, GSE77509, and GSE94660, were obtained from the Gene Expression Omnibus database, and one RNA-seq raw dataset was acquired from The Cancer Genome Atlas (TCGA). Overall, 103 genes were up-regulated and 127 were down-regulated. A protein–protein interaction (PPI) network was established using Cytoscape software, and 12 pivotal genes were selected as hub genes. The 230 differentially expressed genes and 12 hub genes were subjected to functional and pathway enrichment analyses, and the results suggested that cell cycle, nuclear division, mitotic nuclear division, oocyte meiosis, retinol metabolism, and p53 signaling-related pathways play important roles in HBV-related HCC progression. Further, among the 12 hub genes, kinesin family member 11 (KIF11), TPX2 microtubule nucleation factor (TPX2), kinesin family member 20A (KIF20A), and cyclin B2 (CCNB2) were identified as independent prognostic genes by survival analysis and univariate and multivariate Cox regression analysis. These four genes showed higher expression levels in HCC than in normal tissue samples, as identified upon analyses with Oncomine. In addition, in comparison with normal tissues, the expression levels of KIF11, TPX2, KIF20A, and CCNB2 were higher in HBV-related HCC than in HCV-related HCC tissues. In conclusion, our results suggest that KIF11, TPX2, KIF20A, and CCNB2 might be involved in the carcinogenesis and development of HBV-related HCC. They can thus be used as independent prognostic genes and novel biomarkers for the diagnosis of HBV-related HCC and development of pertinent therapeutic strategies.https://www.frontiersin.org/article/10.3389/fgene.2020.555537/fullhepatitis B virushepatocellular carcinomahub genesbiomarkersbioinformatics analysis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xian-Chang Zeng Lu Zhang Wen-Jun Liao Lu Ao Ze-Man Lin Wen Kang Wan-Nan Chen Wan-Nan Chen Xu Lin Xu Lin |
spellingShingle |
Xian-Chang Zeng Lu Zhang Wen-Jun Liao Lu Ao Ze-Man Lin Wen Kang Wan-Nan Chen Wan-Nan Chen Xu Lin Xu Lin Screening and Identification of Potential Biomarkers in Hepatitis B Virus-Related Hepatocellular Carcinoma by Bioinformatics Analysis Frontiers in Genetics hepatitis B virus hepatocellular carcinoma hub genes biomarkers bioinformatics analysis |
author_facet |
Xian-Chang Zeng Lu Zhang Wen-Jun Liao Lu Ao Ze-Man Lin Wen Kang Wan-Nan Chen Wan-Nan Chen Xu Lin Xu Lin |
author_sort |
Xian-Chang Zeng |
title |
Screening and Identification of Potential Biomarkers in Hepatitis B Virus-Related Hepatocellular Carcinoma by Bioinformatics Analysis |
title_short |
Screening and Identification of Potential Biomarkers in Hepatitis B Virus-Related Hepatocellular Carcinoma by Bioinformatics Analysis |
title_full |
Screening and Identification of Potential Biomarkers in Hepatitis B Virus-Related Hepatocellular Carcinoma by Bioinformatics Analysis |
title_fullStr |
Screening and Identification of Potential Biomarkers in Hepatitis B Virus-Related Hepatocellular Carcinoma by Bioinformatics Analysis |
title_full_unstemmed |
Screening and Identification of Potential Biomarkers in Hepatitis B Virus-Related Hepatocellular Carcinoma by Bioinformatics Analysis |
title_sort |
screening and identification of potential biomarkers in hepatitis b virus-related hepatocellular carcinoma by bioinformatics analysis |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Genetics |
issn |
1664-8021 |
publishDate |
2020-09-01 |
description |
Hepatocellular carcinoma (HCC) is one of the most lethal cancers globally. Hepatitis B virus (HBV) infection might cause chronic hepatitis and cirrhosis, leading to HCC. To screen prognostic genes and therapeutic targets for HCC by bioinformatics analysis and determine the mechanisms underlying HBV-related HCC, three high-throughput RNA-seq based raw datasets, namely GSE25599, GSE77509, and GSE94660, were obtained from the Gene Expression Omnibus database, and one RNA-seq raw dataset was acquired from The Cancer Genome Atlas (TCGA). Overall, 103 genes were up-regulated and 127 were down-regulated. A protein–protein interaction (PPI) network was established using Cytoscape software, and 12 pivotal genes were selected as hub genes. The 230 differentially expressed genes and 12 hub genes were subjected to functional and pathway enrichment analyses, and the results suggested that cell cycle, nuclear division, mitotic nuclear division, oocyte meiosis, retinol metabolism, and p53 signaling-related pathways play important roles in HBV-related HCC progression. Further, among the 12 hub genes, kinesin family member 11 (KIF11), TPX2 microtubule nucleation factor (TPX2), kinesin family member 20A (KIF20A), and cyclin B2 (CCNB2) were identified as independent prognostic genes by survival analysis and univariate and multivariate Cox regression analysis. These four genes showed higher expression levels in HCC than in normal tissue samples, as identified upon analyses with Oncomine. In addition, in comparison with normal tissues, the expression levels of KIF11, TPX2, KIF20A, and CCNB2 were higher in HBV-related HCC than in HCV-related HCC tissues. In conclusion, our results suggest that KIF11, TPX2, KIF20A, and CCNB2 might be involved in the carcinogenesis and development of HBV-related HCC. They can thus be used as independent prognostic genes and novel biomarkers for the diagnosis of HBV-related HCC and development of pertinent therapeutic strategies. |
topic |
hepatitis B virus hepatocellular carcinoma hub genes biomarkers bioinformatics analysis |
url |
https://www.frontiersin.org/article/10.3389/fgene.2020.555537/full |
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