Transcriptomic identification of HBx-associated hub genes in hepatocellular carcinoma.
Transcriptomic identification of HBx-associated hub genes in hepatocellular carcinoma.
复制标题
肝细胞癌中 HBx 相关 Hub 基因的转录组鉴定
作者：
Ni Z;Lu J;Huang W;Khan H;Wu X;Huang D;Shi G;Niu Y;Huang H
肝细胞癌（HCC）是世界上最常见的恶性肿瘤之一。在涉及肝癌发生的危险因素中，乙型肝炎病毒（HBV） X蛋白（HBx）被认为是肝癌发生的关键调节因子。HBx是否促进或保护HCC仍存在争议，因此探索新的HBx相关基因仍然很重要。HBx在HepG2、HepG2.2.15和SMMC-7721细胞系、原代小鼠肝细胞和C57BL/6N小鼠肝脏中过表达。对HBx过表达的HepG2细胞及相关差异表达基因（DEGs）进行高通量RNA测序分析、途径富集分析、蛋白-蛋白相互作用网络（PPIs）、重叠分析。此外，使用hbv阳性HCC数据集的基因表达Omnibus （GEO）和蛋白质组学数据集来验证所选deg的表达和预后。最后，我们还通过致癌阵列分析评估了HBx已知的致癌作用。从hbx过表达的HepG2细胞中共获得523个deg。在短暂转染HBx的细胞和三个hbv阳性HCC转录谱数据集中鉴定并验证了12个deg。此外，利用Kaplan-Meier绘图仪数据库，进一步分析12种不同基因的表达水平，以预测患者的预后。在鉴定的12个hbx相关枢纽基因中，表达ARG1和TAT的hbv阳性HCC患者表现出良好的总生存期（OS）和无复发生存期（RFS）。因此，ARG1和TAT的表达可能是潜在的预后指标。
Hepatocellular carcinoma (HCC) is one of the most common malignancies around the world. Among the risk factors involved in liver carcinogenesis, hepatitis B virus (HBV) X protein (HBx) is considered to be a key regulator in hepatocarcinogenesis. Whether HBx promotes or protects against HCC remains controversial, therefore exploring new HBx-associated genes is still important. HBx was overexpressed in HepG2, HepG2.2.15 and SMMC-7721 cell lines, primary mouse hepatocytes and livers of C57BL/6N mice. High-throughput RNA sequencing profiling of HepG2 cells with HBx overexpression and related differentially-expressed genes (DEGs), pathway enrichment analysis, protein-protein interaction networks (PPIs), overlapping analysis were conducted. In addition, Gene Expression Omnibus (GEO) and proteomic datasets of HBV-positive HCC datasets were used to verify the expression and prognosis of selected DEGs. Finally, we also evaluated the known oncogenic role of HBx by oncogenic array analysis. A total of 523 DEGs were obtained from HBx-overexpressing HepG2 cells. Twelve DEGs were identified and validated in cells transiently transfected with HBx and three datasets of HBV-positive HCC transcription profiles. In addition, using the Kaplan-Meier plotter database, the expression levels of the twelve different genes were further analyzed to predict patient outcomes. Among the 12 identified HBx-associated hub genes, HBV-positive HCC patients expressing ARG1 and TAT showed a good overall survival (OS) and relapse-free survival (RFS). Thus, ARG1 and TAT expression could be potential prognostic markers.
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