Pan-cancer analysis of the upstream regulator FDX1 in cuproptosis

The global incidence and mortality of cancer continue to rise rapidly, and cancer remains one of the most severe challenges in the field of public health. Several studies have revealed significant differences in FDX1 expression between various tumor cells and normal tissues, suggesting that it may be involved in tumor initiation, progression, and the regulation of malignant phenotypes. FDX1 is an iron-sulfur protein located in the mitochondria that functions in intracellular electron transfer, shuttling electrons from NADPH to mitochondrial cytochrome P450 and participating in steroid, vitamin D, and bile acid metabolism. Research has demonstrated that FDX1 is a key regulator of cuproptosis. When intracellular free copper levels become excessively high, FDX1 reduces Cu²⁺ to the more toxic Cu⁺. Meanwhile, acting as an upstream regulator of lipoylation, FDX1 promotes the lipoylation of enzymes involved in the TCA cycle. These processes ultimately lead to protein aggregation, mitochondrial destabilization, and the induction of cuproptosis.It is therefore necessary to conduct a systematic pan-cancer analysis of FDX1. In our study, we examined the expression differences of FDX1 between various tumor types and normal tissues, as well as its associations with clinical parameters such as tumor stage, to evaluate its diagnostic and prognostic potential. Furthermore, we investigated the relationship between FDX1 and the tumor immune microenvironment, exploring its possibility as a predictive biomarker for immunotherapy.