Genomic analysis uncovers prognostic and immunogenic characteristics of ferroptosis for clear cell renal cell carcinoma

In this study, the characteristic patterns of ferroptosis in clear cell renal cell carcinoma (ccRCC) were systematically investi-gated with the interactions between ferroptosis and the tumor microenvironment (TME). On the mRNA expression profiles of 57 ferroptosis-related genes (FRGs), three ferroptosis pat-terns were constructed, with distinct prognosis and immune cell infiltrations (especially T cells and dendritic cells). The high ferroptosis scores were characterized by poorer prog-nosis, increased T cell infiltration, higher immune and stro-mal scores, elevated tumor mutation burden, and enhanced response to anti-CTLA4 immunotherapy. Meanwhile, the low ferroptosis scores were distinctly associated with enhanced tumor purity and amino acid and fatty acid meta-bolism pathways. Following validation, the ferroptosis score was an independent and effective prognostic factor. Collec-tively, ferroptosis could be involved in the diverse and com-plex TME. Evaluation of the ferroptosis patterns may height-en the comprehension about immune infiltrations in the TME, assisting oncologists to generate individualized immu-notherapeutic strategies.

Automated summary

This study systematically investigated the characteristic patterns of ferroptosis in ccRCC and its interactions with the tumor microenvironment. High ferroptosis scores were associated with poor prognosis, increased T cell infiltration, elevated immune and stromal scores, and enhanced response to anti-CTLA4 immunotherapy, while low ferroptosis scores were linked to enhanced tumor purity and amino acid and fatty acid metabolism pathways. Evaluation of ferroptosis patterns may help oncologists develop personalized immunotherapeutic strategies.