Background
Hepatocellular carcinoma (HCC) is a common malignant tumor. The application of sorafenib has brought good results to the treatment of HCC, but the drug resistance of sorafenib cannot be ignored. Celecoxib can enhance the efficacy of sorafenib, but its mechanism is still unclear. The main purpose of this study is to study the efficacy and related mechanism of celecoxib and sorafenib in the treatment of hepatocellular carcinoma.
Methods
The GSE45340 data set was retrieved from the Gene Expression Database (GEO), and the differentially expressed genes were obtained by GEO2R. Then, the differentially expressed genes were screened, analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), and then analyzed by Protein-Protein Interaction (PPI) network to obtain the hub genes, which were verified in TCGA database.
Results
Through the analysis of GEO2r, we got 2181 differentially expressed genes. We selected 50 of the most diverse genes for go and KEGG enrichment analysis, and obtained their main enrichment pathways. The protein-protein interaction network of 50 genes was further obtained. Thus, the relevant key genes were obtained, and twelve genes were screened. Twelve genes (MCM4, POLA1, MCM6, MCM3, RBBP4, DNA2, AP2B1, KIF11, KIF23, TUBA1B, KIF14, NUDT21) significantly related to the prognosis of HCC and the molecular pathways involved in these genes were screened, which explained how celecoxib enhanced the efficacy of sorafenib. Twelve genes were further enriched and analyzed, and their possible mechanism of action was obtained.
Conclusions
celecoxib combined with sorafenib can enhance the regulation of hepatocellular carcinoma gene and reduce the drug resistance to sorafenib, which is of great significance for the treatment of hepatocellular carcinoma.