Chronic infection with hepatitis B virus (HBV) has long been recognized as a dominant hazard factor for hepatocellular carcinoma (HCC) and accounts for at least half of HCC instances globally. However, the underlying molecular mechanism of HBV-linked HCC has not been completely elucidated. Here, three microarray datasets, totally containing 170 tumoral samples and 181 adjacent normal tissues from the liver of patients suffering from HBV-related HCC assembled from the Gene Expression Omnibus (GEO) database, were subjected to integrated analysis of differentially expressed genes (DEGs). Subsequently, the analysis of function and pathway enrichment as well as the protein-protein interaction network (PPI) was performed. The ten hub genes screened out from the PPI network were further subjected to expression profile and survival analysis. Overall, 329 DEGs (67 upregulated and 262 downregulated) were identified. Ten DEGs with the highest degree of connectivity included cyclin-dependent kinase 1 (CDK1), cyclin B1 (CCNB1), cyclin B2 (CCNB2), PDZ-binding kinase (PBK), abnormal spindle microtubule assembly (ASPM), nuclear division cycle 80 (NDC80), aurora kinase A (AURKA), targeting protein for xenopus kinesin-like protein 2 (TPX2), kinesin family member 2C (KIF2C), and centromere protein F (CENPF). Kaplan-Meier analysis unveiled that overexpression levels of KIF2C and TPX2 were relevant to both the poor overall survival and relapse-free survival. In summary, the hub genes validated in the present study may provide promising targets for the diagnosis, prognosis, and therapy of HBV-associated HCC. Additionally, our work uncovers various crucial biological components (e.g., extracellular exosome) and signaling pathways that participate in the progression of HCC induced by HBV, serving comprehensive knowledge of the mechanisms regarding HBV-related HCC.

中文翻译：

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综合生物信息分析确定了乙型肝炎病毒相关肝细胞癌的网络和有前景的生物标志物。

乙型肝炎病毒 (HBV) 慢性感染长期以来一直被认为是肝细胞癌 (HCC) 的主要危险因素，并且占全球 HCC 病例的至少一半。然而，HBV 相关 HCC 的潜在分子机制尚未完全阐明。这里，从基因表达综合（GEO）数据库中收集了三个微阵列数据集，总共包含 170 个来自 HBV 相关 HCC 患者肝脏的肿瘤样本和 181 个邻近正常组织，对差异表达基因（DEG）进行了整合分析。随后，进行了功能和通路富集以及蛋白质-蛋白质相互作用网络（PPI）的分析。从PPI网络中筛选出的10个枢纽基因进一步进行表达谱和生存分析。总体而言，确定了 329 个 DEG（67 个上调和 262 个下调）。连接程度最高的 10 个 DEG 包括细胞周期蛋白依赖性激酶 1 (CDK1)、细胞周期蛋白 B1 (CCNB1)、细胞周期蛋白 B2 (CCNB2)、PDZ 结合激酶 (PBK)、异常纺锤体微管组装 (ASPM)、核分裂周期 80 (NDC80)、极光激酶 A (AURKA)、爪蟾驱动蛋白样蛋白 2 (TPX2)、驱动蛋白家族成员 2C (KIF2C) 和着丝粒蛋白 F (CENPF) 的靶向蛋白。Kaplan-Meier 分析揭示，KIF2C 和 TPX2 的过度表达水平与较差的总生存期和无复发生存期相关。总之，本研究中验证的中心基因可能为 HBV 相关 HCC 的诊断、预后和治疗提供有希望的靶点。此外，我们的工作揭示了参与 HBV 诱导的 HCC 进展的各种关键生物成分（例如细胞外外泌体）和信号通路，为 HBV 相关 HCC 的机制提供了全面的了解。