SFN Correlated with Hepatocellular Carcinoma Prognosis and Sorafenib Resistance Predicted by Bioinformatics Analysis
Stratifin (SFN) is a novel prognostic factor in many human cancers. However, the outcome of SFN dysfunction and the molecular process governing the dysfunction of SFN in hepatocellular carcinoma (HCC) are unknown. In this study, bioinformatics analysis was used to analyze SFN mRNA and protein expression in HCC patients in the Gene Expression Profiling Interactive Analysis (GEPIA) and Human Protein Atlas databases. The correlation between SFN expression and prognosis and pathological staging in HCC patients was evaluated by using the GEPIA database. The network of SFN protein interactions was predicted by using the STRING database. SFN gene mutations, promoter methylation levels, and miRNAs binding to SFN were analyzed by using the cBioPortal, MethHC, GCBI and starBase databases. The results indicated that SFN mRNA transcripts were upregulated in HCC and most other tumors. SFN protein levels were increased in HCC tissues compared with paired normal liver tissues. Additionally, the staining intensity and positive rates of SFN protein were higher in cholangiocarcinoma than in HCC. The higher levels of SFN were related to a poor prognosis in HCC patients. The expression of SFN mRNA was significantly increased in HCC patients with sorafenib resistance compared with the untreated group. Moreover, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the proteins interacting with SFN are mainly involved in the cell cycle and the PI3K-AKT signaling pathway. The methylation levels of the SFN promoter region were significantly downregulated in HCC tissues compared with normal liver tissues and negatively correlated with SFN expression. Conclusion: These data provide the first evidence that SFN is strongly correlated with HCC prognosis and sorafenib resistance. These findings also provide new insights suggesting that SFN could become a potential novel marker for HCC.