Hepatocellular carcinoma (HCC) is an aggressive malignancy, and CCL18, a marker of M2 macrophage activation, is often associated with tumor immune suppression. However, the role of CCL18 and its signaling pathway in HCC is still limited. Our study focuses on investigating the prognostic impact of CCL18 and its signaling pathway in HCC patients and biological functions
HCC-related RNA-seq data were obtained from TCGA, ICGC, and GEO. The 6 hub genes with the highest correlation to prognosis were identified using univariate Cox and LASSO regression analysis. Multivariate Cox regression analysis was performed to assess their independent prognostic potential and a nomogram was constructed.
We identified 6 survival-related genes (BMI1, CCR3, CDC25C, CFL1, LDHA, RAC1) within the CCL18 signaling pathway in HCC patients. A nomogram was constructed using the TCGA_LIHC cohort to predict patient survival probability. Exogenous CCL18, as well as overexpression of BMI1, CCR3, CDC25C, CFL1, LDHA, and RAC1, can promote proliferation, migration, invasion, stemness, and increased expression of PD-L1 protein in LM3 and MHCC-97H cell lines. In the high-risk group of patients from the TCGA_LIHC cohort, immune suppression was observed, with a strong correlation to 21 immune-related genes and suppressive immune cells.
Exogenous CCL18 promotes LM3 and MHCC-97H cells proliferation, migration, invasion, stemness, and immune evasion. The high expression of BMI1, CCR3, CDC25C, CFL1, LDHA, and RAC1 can serve as a biomarkers for immune evasion in HCC.