Background: Hepatocellular carcinoma (HCC) is one of the most common human malignant tumors. The prognosis of HCC patients is still unsatisfying. In this study, we performed the integrated bioinformatics analysis to identify potential biomarkers and biological pathways in HCC.
Methods: Gene expression profiles were obtained from the Gene Expression Omnibus database (GSE55048, GSE55758, and GSE56545) for the screening of the common differentially expressed genes (DEGs) between HCC tissues and matched non-tumor tissues. DEGs were subjected to Gene Ontology, KEGG pathway, and Reactome pathway analysis. The hub genes were identified by using protein–protein interaction (PPI) network analysis. The hub genes in HCC were further subjected to overall survival analysis of HCC patients. The hub genes were further validated by in vitro functional assays.
Results: A total of 544 common differentially expressed genes were screened from three datasets. Gene Ontology, KEGG and Reactome analysis results showed that DEGs are significantly associated with the biological process of cell cycle, cell division, and DNA replication. PPI network analysis identified 20 hub genes from the DEGs. These hub genes except CENPE were all significantly up-regulated in the HCC tissues when compared to non-tumor tissues. The Kaplan–Meier survival analysis results showed that the high expression of the 20 hub genes was associated with shorter survival of the HCC patients. Further validation studies showed that knockdown of KIF14  and KIF23  both suppressed the proliferative potential, increased the caspase-3/-7 activity, up-regulated Bax expression, and promoted the invasive and migratory abilities in the HCC cells. In addition, knockdown of KIF14  and KIF23  enhanced chemosensitivity to cisplatin and sorafenib in the HCC cells. Finally, the high expression of KIF14  and KIF23  was associated with shorter progression-free survival, recurrence-free survival, and disease-specific survival of patients with HCC.
Conclusion: In conclusion, the present study performed the integrated bioinformatics analysis and showed that KIF14  and KIF23  silence attenuated cell proliferation, invasion, and migration, and promoted chemosensitivity of HCC cells. KIF14  and KIF23  may serve as potential biomarkers for predicting the worse prognosis of patients with HCC.
Keywords: hepatocellular carcinoma, differentially expressed genes, hub genes, KIF14 , KIF23 , survival analysis