Prognostic potential and mechanism of SORT1 and its co‐expressed genes in hepatocellular carcinoma based on integrative analysis of multiple database

Abnormal SORT1 expression has been reported in various cancers. However, the expression and function of SORT1 in hepatocellular carcinoma (HCC) remain to be explored. This study aims to explore the expression and function of SORT1 and to identify its co‐expressed genes in HCC. Various gene expression databases were applied in our analysis. We found SORT1 was up‐regulated in HCC tumor tissues and high SORT1 expression level was associated with worse overall survival (OS). Co‐expressed genes with SORT1 and its potential regulators were explored using LinkedOmics. Functional network analysis of co‐expressed genes by Metascape revealed that they participated in aberrant lipid metabolism, AMPK signaling pathway, and PPAR signaling pathway which were all strongly linked to the pathogenesis of HCC. In addition, co‐expression genes were analyzed by Cytoscape to identify their hub genes, which included CYB5A, CYP2C9, CYP3A5, CYP4A11, and POR. The mRNA expression level of CYP2C9, CYP3A5, and CYP4A11 were down‐regulated in HCC tumor tissues via GEPIA. High hub genes expression level was associated with better OS and progression free survival (PFS) in HCC. The correlations between SORT1 and hub genes with cancer immune infiltrates were investigated by TIMER. Notably, SORT1 and hub genes expression was positively correlated with infiltrating levels of different immune cells. Our findings suggested that high SORT1 expression level predicted dismal prognosis in HCC and its possible mechanism was immune‐related.