C chemokines are prognostic biomarkers correlated with diverse immune cell infiltrations in clear cell renal cell carcinoma

BACKGROUND: The interplay between tumor-infiltrating immune cells and cancer cells affects cancer initiation, progression, and treatment. C chemokines are critically involved in immune cell chemotaxis, self-tolerance formation, antigen cross-presentation, and cytotoxic immune response. However, their roles in cancer development are still largely unknown. METHODS: We comprehensively analyzed the expression, prognostic value, functions, and immune implication of C chemokines in clear cell renal cell carcinoma (ccRCC) using multiple databases. Besides, we detected the expression of C chemokines in RCC cell lines using quantitative real-time polymerase chain reaction (qPCR). RESULTS: Through analyzing The Cancer Genome Atlas (TCGA), Oncomine and Gene Expression Omnibus (GEO) ccRCC datasets, we found that C chemokines were significantly upregulated in ccRCC tumor tissues and associated with tumor progression. Besides, qPCR revealed the overexpression of C chemokines in RCC cell lines. Promoter hypomethylation was a potential factor causing the upregulation of C chemokines. ccRCC patients with higher levels of C chemokines had significantly poorer overall survival (OS), progression-free interval (PFI), and disease-specific survival (DSS). C chemokines and related genes were involved mainly in cytokine-cytokine receptor interactions and the chemokine signaling and Toll-like receptor signaling pathways. Correlation analysis revealed a positive correlation between C chemokines and the infiltration of 25 immune cell subtypes, many of which affected the prognosis of ccRCC. Moreover, C chemokines were positively correlated with the expression of genes associated with M2 macrophage polarization and T-cell exhaustion, and the expression of several immune checkpoints in ccRCC. CONCLUSIONS: Our research provides preliminary insights into the prognostic value and immune implication of C chemokines in ccRCC, which is conducive to the prediction of survival and immunotherapy response, and the development of novel therapeutic targets for ccRCC.