The last decade has witnessed revolutionary advances taken in
immunotherapy for various malignant
tumors. However, immune-related molecules and their characteristics in the prediction of clinical outcomes and
immunotherapy response in
clear cell renal cell carcinoma (ccRCC) remain largely unclear. C-C Motif
Chemokine Ligand 4 (CCL4) was extracted from the intersection analysis of common differentially expressed genes (DEGs) of four microarray datasets from the Gene Expression Omnibus database and immune-related gene lists in the ImmPort database using Cytoscape plug-ins and univariate Cox regression analysis. Subsequential analysis revealed that CCL4 was highly expressed in ccRCC patients, and positively correlated with multiple clinicopathological characteristics, such as grade, stage and
metastasis, while negatively with overall survival (OS). We performed gene set enrichment analysis (GSEA) and gene set variant analysis (GSVA) with gene sets coexpressed with CCL4, and observed that gene sets positively related to CCL4 were enriched in
tumor proliferation and immune-related pathways while metabolic activities in the negatively one. To further explore the correlation between CCL4 and immune-related biological process, the CIBERSORT algorithm, ESTIMATE method, and
tumor mutational burden (TMB) score were employed to evaluate the tumor microenvironment (TME) characteristics of each sample and confirmed that high CCL4 expression might give rise to high immune cell infiltration. Moreover, correlation analysis revealed that CCL4 was positively correlated with common immune checkpoint genes, such as
programmed cell death protein 1 (PD-1), cytotoxic T-lymphocyte-associated
protein 4 (CTLA4), and lymphocyte activating 3 (LAG3). Overall, this study demonstrated that CCL4 might serve as a potential immune-related prognostic
biomarker to predict clinical outcomes and
immunotherapy response in ccRCC. Moreover, CCL4 might contribute to TME modulation, indicating the mechanism CCL4 involved in
tumor proliferation and
metastasis, which could provide novel therapeutic perceptions for ccRCC patients.