Comprehensive Network Analysis of the Molecular Mechanisms Associated with Sorafenib Resistance in Hepatocellular Carcinoma

Abstract

Background: This research aimed to investigate the potential molecular mechanism of sorafenib resistance to hepatocellular carcinoma (HCC). Methods: Differential expression analysis were performed to identified differentially expressed genes (DEGs) in sorafenib resistant HCC. Then, a series of bioinformatic analysis were performed to explore the potential crucial molecules in sorafenib resistant HCC. For example, gene function annotation, pivot regulators prediction, ROC analysis and survival analysis. Results: There were 827 differentially expressed genes were identified. Moreover, most of the differentially expressed genes are involved in immune and inflammatory-related functions and signaling pathways. Also, 18 transcription factors were predicted to regulate the transcription factors of differentially expressed genes, which play an essential role in the regulation of dysfunctional gene networks. In target genes of transcription factors, CDK1 and CDKN1A have high diagnostic value in the resistance of hepatocellular carcinoma to sorafenib. Conclusions: TAPBP has the strongest correlation with drug resistance of hepatocellular carcinoma and the highest diagnostic efficiency. In addition, CDK1 and CDKN1A have high diagnostic value in the resistance of hepatocellular carcinoma to sorafenib. Overall, our analysis shows that a large number of gene disorders occur during the development of resistance to sorafenib in hepatocellular carcinoma, and they are associated with immune and inflammatory reactions in the body. These results provide critical theoretical references for the pathogenesis and diagnosis of sorafenib resistance.