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Background  Clear cell renal cell carcinoma (ccRCC) remains a common malignancy in the urinary system. Although dramatic progress was made in multimodal therapies, the improvement of its prognosis continues to be unsatisfactory. The antibody-binding crystallizable fragment (Fc) γ receptors (FcγRs) are expressed on the surface of leukocytes, to mediate antibody-induced cell-mediated anti-tumor responses when tumor-reactive antibodies are present. FcγRs have been studied extensively in immune cells, but rarely in cancer cells.    Methods  ONCOMINE, UALCAN, GEPIA, TIMER, TISIDB, Kaplan–Meier Plotter, SurvivalMeth, and STRING databases were utilized in this study.    Results  Transcriptional levels of FcγRs were upregulated in patients with ccRCC. There was a noticeable correlation between the over expressions of FCGR1A/B/C, FCGR2A, and clinical cancer stages/tumor grade in ccRCC patients. Besides, higher transcription levels of FcγRs were found to be associated with poor overall survival (OS) in ccRCC patients. Further, high DNA methylation levels of FcγRs were also observed in ccRCC patients, and higher DNA methylation levels of FcγRs were associated with shorter OS. Moreover, we also found that the expression of FcγRs was significantly correlated with immune infiltrates, namely, immune cells (NK, macrophages, Treg, cells) and immunoinhibitor (IL-10, TGFB1, and CTLA-4).    Conclusions  Our study demonstrated that high DNA methylation levels of FcγRs lead to their low mRNA, protein levels, and poor prognosis in ccRCC patients, which may provide new insights into the choice of immunotherapy targets and prognostic biomarkers.

Systematic Analysis of the Expression and Prognosis of Fcγ Receptors in Clear Cell Renal Cell Carcinoma