Hepcidin as a prognostic biomarker in clear cell renal cell carcinoma

Clear cell renal cell carcinoma (ccRCC) is a common malignancy of urologic neoplasms. Hepcidin is a pivotal modulator of iron metabolism involved in human cancers; however, the biological significance of hepcidin in ccRCC remains to be fully understood. Therefore, in this study, we evaluated the expression profiles of hepcidin in ccRCC from several public databases and found that hepcidin expression was upregulated in ccRCC, which was further validated in ccRCC cell lines, clinical samples, and tissue microarray (TMA) quantitative real-time PCR and immunohistochemistry. In addition, we found that the expression level of hepcidin was correlated with the age, T stage and pathologic stage of patients. Furthermore, hepcidin promoter methylation was significantly associated with the worse poor clinical parameters of ccRCC patients, and hepcidin was an independent prognostic factor. Mechanistically, enrichment analysis revealed that hepcidin participated in the immune-related and metabolism-related pathways. Hepcidin was positively correlated with not only immune infiltration and immune checkpoints but also tumor mutation burden and cytotoxic T lymphocyte. Finally, we validated the positive correlation of hepcidin with the marker of macrophage (CD68) in the TMA. Our findings provide insights into understanding the function and its underlying mechanism of hepcidin in ccRCC and suggest that hepcidin might serve as a potential predictive biomarker of response to immunotherapy and the prognosis of patients with ccRCC.