Dataset Information

HBV integrated genomic characterization revealed hepatocyte genomic alterations in HBV-related hepatocellular carcinomas.

ABSTRACT: Hepatocellular carcinoma (HCC) is one of the most lethal malignancies that is closely associated with the Hepatitis B virus (HBV). HBV integration into host genomes can induce instability and the aberrant expression of human genomic DNA. To directly assess HBV integration breakpoints at whole genome level, four small sequencing libraries were constructed and the HBV integration profiles of four patients with HCC were characterized. In total, the current study identified 11,800,974, 11,216,998, 11,026,546 and 11,607,842 clean reads for patients 1-3 and 4, respectively, of which 92.82, 95.95, 97.21 and 97.29% were properly aligned to the hybrid reference genome. In addition, 220 HBV integration events were detected from the tumor tissues of four patients with HCC and an average of 55 breakpoints per sample was calculated. The results indicated that HBV integration events may be implicated in HCC physiologies and diseases. The results acquired may also provide insight into the pathogenesis of HCC, which may be valuable for future HCC therapy.

SUBMITTER: Yang M

PROVIDER: S-EPMC7549396 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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HBV integrated genomic characterization revealed hepatocyte genomic alterations in HBV-related hepatocellular carcinomas.

Yang Ming M Yang Guiqi G Li Fengyan F Ou Minglin M Li Chunhong C Chen Jiejing J Lin Hua H Zhang Yue Y Xue Wen W Wu Yan Y Xu Yong Y Sui Weiguo W Dai Yong Y

Molecular and clinical oncology 20201001 6

Hepatocellular carcinoma (HCC) is one of the most lethal malignancies that is closely associated with the Hepatitis B virus (HBV). HBV integration into host genomes can induce instability and the aberrant expression of human genomic DNA. To directly assess HBV integration breakpoints at whole genome level, four small sequencing libraries were constructed and the HBV integration profiles of four patients with HCC were characterized. In total, the current study identified 11,800,974, 11,216,998, 1 ...[more]

PMID: 33062269

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Project description:BackgroundIncreasing evidence demonstrated that long noncoding RNA (lncRNA) could affect inflammatory tumor immune microenvironment by modulating gene expression and could be used as a biomarker for HBC-related hepatocellular carcinoma (HCC) but still needs further research. The aim of the present study was to determine an lncRNA signature for the diagnosis of HBV-related HCC.MethodsHBV-related HCC expression profiles (GSE55092, GSE19665, and GSE84402) were abstracted from the GEO (Gene Expression Omnibus) data resource, and R package limma and RobustRankAggreg were employed to identify common differentially expressed genes (DEGs). Using machine learning, optimal diagnostic lncRNA molecular markers for HBV-related HCC were identified. The expression of candidate lncRNAs was cross-validated in GSE121248, and an ROC (receiver operating characteristic) curve of lncRNA biomarkers was carried out. Additionally, a coexpression network and functional annotation was built, after which a PPI (protein-protein interaction) network along with module analysis were conducted with the Cytoscape open source software.ResultA total of 38 DElncRNAs and 543 DEmRNAs were identified with a fold change larger than 2.0 and a P value < 0.05. By machine learning, AL356056.2, AL445524.1, TRIM52-AS1, AC093642.1, EHMT2-AS1, AC003991.1, AC008040.1, LINC00844, and LINC01018 were screened out as optional diagnostic lncRNA biosignatures for HBV-related HCC. The AUC (areas under the curve) of the SVM (support vector machine) model and random forest model were 0.957 and 0.904, respectively, and the specificity and sensitivity were 95.7 and 100% and 94.3 and 86.5%, respectively. The results of functional enrichment analysis showed that the integrated coexpressed DEmRNAs shared common cascades in the p53 signaling pathway, retinol metabolism, PI3K-Akt signaling cascade, and chemical carcinogenesis. The integrated DEmRNA PPI network complex was found to be comprised of 87 nodes, and two vital modules with a high degree were selected with the MCODE app.ConclusionThe present study identified nine potential diagnostic biomarkers for HBV-related HCC, all of which could potentially modulated gene expression related to inflammatory conditions in the tumor immune microenvironment. The functional annotation of the target DEmRNAs yielded novel evidence in evaluating the precise functions of lncRNA in HBV-related HCC.

Dataset Information

HBV integrated genomic characterization revealed hepatocyte genomic alterations in HBV-related hepatocellular carcinomas.

Publications

HBV integrated genomic characterization revealed hepatocyte genomic alterations in HBV-related hepatocellular carcinomas.

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