Abstract
As a type of regulated cell death induced by Ras selective lethal (RSL) compounds such as erasti, ferroptosis is characterized by iron-dependent lipid peroxide accumulation to lethal levels. At present, little is known about the role of ferroptosis-related genes in clear-cell renal cell carcinoma (ccRCC). In the present study, the expression data of ferroptosis-related genes in ccRCC were obtained from the Cancer Genome Atlas (TCGA), and COX regression analysis was performed to construct a risk model of ferroptosis prognostic signature. The GEO database was used to verify the accuracy of the model. The following findings were made: the results reveal that the prognostic signature constructed by 11 ferroptosis genes (CARS, CD44, DPP4, GCLC, HMGCR, HSPB1, NCOA4, SAT1, PHKG2, GOT1, HMOX1) was significantly related to the overall survival (OS) of ccRCC patients based on the lowest Akaike information criterion (AIC); multivariate analysis indicates that ferroptosis-related gene prognostic signature was an independent prognostic factor in ccRCC patients; the calibration curve and c-index value (0.77) demonstrate that the nomogram with the signature could predict the survival of ccRCC patients; and enrichment analysis shows that the high-risk group were enriched in humoral immunity and receptor interaction pathways. The aforementioned findings indicate that the ferroptosis-related gene signature can accurately predict the prognosis of ccRCC patients and provide valuable insights for individualized treatment.
Highlights
Renal cell carcinoma (RCC), known as renal cell adenocarcinoma, is one of the most common malignant tumors, with an incidence of about 3% of all adult malignancies [1] and more than 90% of primary renal tumors and pelvic cancer [2]. clear-cell renal cell carcinoma is the most common subtype of renal cell carcinoma, accounting for 70–80% of renal cell carcinoma and has the highest mortality rate [3]
Multivariate Cox regression analysis indicated that 11 out of 27 ferroptosis-related genes were the best candidates to construct the prognosis signature based on the lowest Akaike information criterion (AIC)
Ferroptosis is a recently defined, non-apoptotic, regulated cell death process that comprises abnormal metabolism of cellular lipid oxides catalyzed by iron ions or iron-containing enzymes [23]
Summary
Renal cell carcinoma (RCC), known as renal cell adenocarcinoma, is one of the most common malignant tumors, with an incidence of about 3% of all adult malignancies [1] and more than 90% of primary renal tumors and pelvic cancer [2]. clear-cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma, accounting for 70–80% of renal cell carcinoma and has the highest mortality rate [3]. More than 100,000 renal cell carcinoma patients die each year due Ferroptosis-Related Prognosis Signature to cancer progression [6]. Ferroptosis is an iron-dependent form of regulated cell death, which is driven by the lethal accumulation of lipid peroxidation [8]. It is a novel death phenotype distinct from apoptosis, various forms of necrosis or autophagy [9]. Glutathione is essential to prevent ferroptosis caused by impaired clear cell lipid metabolism [14]. Inhibition of b-oxidation and reduced fatty acid metabolism makes renal cancer cells highly dependent on GSH/GPX pathway to prevent lipid peroxidation and cell ferroptotic death [15]. Induction of ferroptosis has become a promising treatment for ccRCC
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