Hepatocellular Carcinoma Subtyping and Prognostic Model Construction Based on Chemokine-Related Genes.

ABSTRACT

BACKGROUND: Chemokines not only regulate immune cells but also play significant roles in development and treatment of tumors and patient prognoses. However, these effects have not been fully explained in hepatocellular carcinoma (HCC). MATERIALS AND METHODS: We conducted a clustering analysis of chemokine-related genes. We then examined the differences in survival rates and analyzed immune levels using single-sample Gene Set Enrichment Analysis (ssGSEA) for each subtype. Based on chemokine-related genes of different subtypes, we built a prognostic model in The Cancer Genome Atlas (TCGA) dataset using the survival package and glmnet package and validated it in the Gene Expression Omnibus (GEO) dataset. We used univariate and multivariate regression analyses to select independent prognostic factors and used R package rms to draw a nomogram reflecting patient survival rates at 1, 3, and 5 years. RESULTS: We identified two chemokine subtypes and, after screening, found that Cluster1 had higher survival rates than Cluster2. In addition, in terms of immune evaluation, stromal evaluation, ESTIMATE evaluation, immune abundance, immune function, and expressions of various immune checkpoints, immune levels of Cluster1 were significantly better than those of Cluster2. The immunophenoscore (IPS) of HCC patients in Cluster1 was significantly higher than that in Cluster2. Furthermore, we established a prognostic model consisting of 9 genes, which correlated with chemokines. Through testing, Riskscore was revealed as an independent prognostic factor, and the model could effectively predict HCC patients' prognoses in both TCGA and GEO datasets. CONCLUSION: This study resulted in the development of a novel prognostic model related to chemokine genes, providing new targets and theoretical support for HCC patients.