Hepatocellular carcinoma (HCC) is the fifth most common cancer and one of the leading causes of cancer-related death in the world. Due to the recurrence of HCC, its survival rate is still low. Therefore, it is vital to seek prognostic biomarkers for HCC. In this study, differential analysis was conducted on gene expression data in The Cancer Genome Atlas -LIHC, and 4482 differentially expressed genes in tumor tissue were selected. Then, weighted gene co-expression network analysis was used to analyze the co-expression of the gained differential genes. By module–trait correlation analysis, the turquoise gene module that was significantly related to tumor grade, pathologic_T stage, and clinical stage was identified. Thereafter, enrichment analysis of genes in this module uncovered that the genes were mainly enriched in the signaling pathways involved in spliceosome and cell cycle. After that, through correlation analysis, 18 hub genes highly correlated with tumor grade, clinical stage, pathologic_T stage, and the turquoise module were selected. Meanwhile, protein–protein interaction (PPI) network was constructed by using genes in the module. Finally, three key genes, heterogeneous nuclear ribonucleoprotein L, serrate RNA effector molecule, and cyclin B2, were identified by intersecting the top 30 genes with the highest connectivity in PPI network and the previously obtained 18 hub genes in the turquoise module. Further survival analysis revealed that high expression of the three key genes predicted poor prognosis of HCC. These results indicated the direction for further research on clinical diagnosis and prognostic biomarkers of HCC.

肝细胞癌 (HCC) 是世界上第五大最常见的癌症，也是导致癌症相关死亡的主要原因之一。由于HCC的复发，其存活率仍然很低。因此，寻找HCC的预后生物标志物至关重要。本研究对The Cancer Genome Atlas -LIHC中的基因表达数据进行差异分析，筛选出肿瘤组织中4482个差异表达基因。然后，加权基因共表达网络分析用于分析获得的差异基因的共表达。通过模块-性状相关分析，确定了与肿瘤分级、病理_T分期和临床分期显着相关的绿松石基因模块。此后，对该模块中的基因进行富集分析发现，这些基因主要富集在参与剪接体和细胞周期的信号通路中。之后，通过相关性分析，筛选出与肿瘤分级、临床分期、病理_T分期、turquoise模块高度相关的18个hub基因。同时，利用模块中的基因构建蛋白质-蛋白质相互作用（PPI）网络。最后，通过将 PPI 网络中连接性最高的 30 个基因与之前获得的 turquoise 模块中的 18 个枢纽基因相交，鉴定出三个关键基因，即异质核核糖核蛋白 L、锯齿状 RNA 效应分子和细胞周期蛋白 B2。进一步的生存分析表明，三个关键基因的高表达预示着HCC的不良预后。