Analysis of the expression and prognosis of PCSK9 in human hepatocellular carcinoma

This study investigated the role of PCSK9 in hepatocellular carcinoma(HCC) to identify new diagnostic and treatment targets. We analyzed The Cancer Genome Atlas(TCGA) data from 374 HCC tumors and 50 normal tissues for PCSK9 expression: used Genotype-Tissue Expression Project(GTEx) for survival and staging correlations; assessed immune cell infiltration via CIBERSORT and TIMER; performed Gene Set Enrichment Analysis (GSEA) for PCSK9-related pathways; examined PCSK9 expression in tissues from 26 HCC patients through Immunohistochemical(IHC) and Western blot(WB); created PCSK9 knockout Hep3B cell lines to evaluate proliferation, invasion, migration, and apoptosis; and established a nude mouse model to measure tumor size and PCSK9 expression in xenografts. (1) Patients were divided into high and low PCSK9 expression groups on the basis of TCGA data, with lower PCSK9 levels in normal tissues and higher PCSK9 levels in tumors, and no significant correlation with the clinical stage of HCC. (2) Using CIBERSORT, patients were categorized by PCSK9 levels, revealing significant associations with immune cell infiltration, where high expression correlated with increased levels of several immune cells, whereas others showed lower infiltration in the high-expression group; TIMER results indicated positive correlations among various immune cells and their relationship with HCC survival rates. (3) GSEA indicated that genes with high PCSK9 expression are associated with cholesterol metabolism, cell cycle regulation, and DNA repair, among other pathways. PCSK9 is elevated in HCC, is linked to immune infiltration and pathways, and provides new markers and targets for diagnosis and treatment.