通過生物信息學分析篩选和鑑定乙型肝炎病毒相關肝細胞癌

StephenW

Screening and Identification of Potential Biomarkers in Hepatitis B Virus-Related Hepatocellular Carcinoma by Bioinformatics Analysis
Xian-Chang Zeng  1 , Lu Zhang  1 , Wen-Jun Liao  1 , Lu Ao  2 , Ze-Man Lin  2 , Wen Kang  1 , Wan-Nan Chen  1   3 , Xu Lin  1   3
Affiliations
Affiliations

    1
    Key Laboratory of Gastrointestinal Cancer, Ministry of Education, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China.
    2
    Fujian Key Laboratory of Medical Bioinformatics, Department of Bioinformatics, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China.
    3
    Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University, Fuzhou, China.

    PMID: 33193629 PMCID: PMC7556301 DOI: 10.3389/fgene.2020.555537

Free PMC article
Abstract

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.

Keywords: bioinformatics analysis; biomarkers; hepatitis B virus; hepatocellular carcinoma; hub genes.

Copyright © 2020 Zeng, Zhang, Liao, Ao, Lin, Kang, Chen and Lin.

StephenW

通過生物信息學分析篩选和鑑定乙型肝炎病毒相關肝細胞癌的潛在生物標誌物
曾憲昌1，張魯1，廖文俊1，魯敖2，林則滿2，文康1，陳萬南1 3，徐林1 3
隸屬關係
隸屬關係

    1個
    福建醫科大學基礎醫學院，胃腸道腫瘤教育部重點實驗室，福州
    2
    福建醫科大學基礎醫學學院生物信息學系福建省醫學生物信息學重點實驗室，福州。
    3
    福建醫科大學醫學微生物學系福建省腫瘤微生物學重點實驗室，福州。

    PMID：33193629 PMCID：PMC7556301 DOI：10.3389 / fgene.2020.555537

免費PMC文章
抽象

肝細胞癌（HCC）是全球最致命的癌症之一。乙型肝炎病毒（HBV）感染可能會導致慢性肝炎和肝硬化，從而導致HCC。為了通過生物信息學分析篩選HCC的預後基因和治療靶標並確定HBV相關HCC的潛在機制，從Gene Expression Omnibus數據庫獲得了三個基於高通量RNA-seq的原始數據集，即GSE25599，GSE77509和GSE94660，並且從The Cancer Genome Atlas（TCGA）獲得了一個RNA-seq原始數據集。總體而言，上調了103個基因，下調了127個基因。使用Cytoscape軟件建立了蛋白質-蛋白質相互作用（PPI）網絡，並選擇了12個關鍵基因作為中樞基因。對230個差異表達基因和12個中樞基因進行了功能和途徑富集分析，結果表明細胞週期，核分裂，有絲分裂，核分裂，卵母細胞減數分裂，視黃醇代謝和p53信號相關的途徑在乙肝病毒中起重要作用。相關的肝癌進展。此外，在12個中心基因中，通過生存分析，單變量和單因素分析，驅動蛋白家族成員11（KIF11），TPX2微管成核因子（TPX2），驅動蛋白家族成員20A（KIF20A）和細胞週期蛋白B2（CCNB2）被確定為獨立的預後基因。多元Cox回歸分析。如用Oncomine分析所確定的，這四個基因在HCC中的表達水平高於正常組織樣品中的表達水平。另外，與正常組織相比，HBV相關的HCC中的KIF11，TPX2，KIF20A和CCNB2的表達水平高於HCV相關的HCC組織。總之，我們的結果表明，KIF11，TPX2，KIF20A和CCNB2可能與HBV相關HCC的癌變和發展有關。因此，它們可以用作獨立的預後基因和新穎的生物標誌物，用於診斷HBV相關的HCC和製定相關的治療策略。

關鍵詞：生物信息學分析；生物標誌物乙型肝炎病毒;肝細胞癌；中心基因。

版權所有©2020曾，張，廖，敖，林，康，陳和林。

StephenW

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