Identification of Three Key Genes Associated with Hepatocellular Carcinoma Progression Based on Co-expression Analysis

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.