To investigate the expression of cholesteryl ester transfer protein (CETP) in primary liver cancer (PLC) and evaluate its effect on prognosis and immunity.

The immune-related genes (IRGs) were downloaded from the Gene Expression Omnibus (GEO) datasets including GSE101685, GSE45267 and GSE62232 and ImmPort database. The down-regulated differentially-expressed genes (DEGs) were screened and the unstudied CETP was selected. The expression of CETP in PLC and its association with prognosis of PLC patients were analyzed using UALCAN and Kaplan-Meier Plotter databases, respectively. LinkedOmics database was employed for gene ontology (GO) analysis and KEGG pathway enrichment analysis. Timer and TISIDB databases were adopted to analyze the correlation between CETP and immune cell infiltration and immunomodulators of PLC.

16 DEGs were screened from 3 liver cancer datasets and ImmPort database, and the down-regulated key gene of CETP was selected. According to the UALCAN database, the expression level of CETP genes in PLC tissues was lower than that in normal tissues (P<0.05). The expression level of CETP genes was intimately correlated with the American Joint Committee on Cancer (AJCC) staging and lymph node metastasis (P<0.05). Kaplan-Meier Plotter database analysis showed that the median survival of patients with low expression of CETP genes was 37.8 months, significantly shorter than 61.7 months of that with high expression of CETP genes (HR=0.66, P<0.05). GO analysis revealed that CETP-related genes were mainly involved in immune response, leukocyte adhesion, cell death and cell chemotaxis, etc. KEGG pathway analysis showed that CETP gene was enriched in NK cell-mediated cytotoxicity, cytokine-cytokine receptor interaction, oxidative phosphorylation, Th1 and Th2 cell differentiation and other signaling pathways. TIMER and TISIDB databases showed that CETP was associated with the infiltration levels of dendritic cells and CD8⁺T cells, and immunomodulators in PLC.

Online database analysis indicates that the expression level of CETP genes is down-regulated in PLC. Low expression of CETP genes is correlated with clinical characteristics and poor prognosis of patients. The changes of CETP genes expression can affect immune response, thereby probably affecting clinical prognosis of PLC patients.