Cuproptosis key gene FDX1 is a prognostic biomarker and associated with immune infiltration in glioma

Abstract

Recent studies have found that the protein encoded by the FDX1 gene is involved in mediating Cuproptosis as a regulator of protein lipoylation and related to immune response process of tumors. However, the specific biological function of FDX1 in glioma is currently unclear. To explore the potential function of FDX1, this study explored the correlation between the expression of FDX1 in cancers and survival prognosis by analyzing the public databases of GEPIA and Cbioportal. Immune infiltration was analyzed by the TIMER2.0 database in tumors. The possible biological processes and functions of FDX1-related in glioma were annotated through gene enrichment. Relationship between Cuproptosis and autophagy was explored through gene co-expression studies. Summary and conclusions of this study: (1) FDX1 is highly expressed in gliomas and associated with poor prognosis in low-grade gliomas (LGG). (2) Gene annotation indicates that FDX1 is mainly involved in the tumor protein lipoylation and cell death. (3) FDX1 expression is positively correlated with the infiltration of immune cells. (4) LIPT2 and NNAT, two other genes involved in lipoylation, may be unidentified marker gene for Cuproptosis. And the Cuproptosis genes related to FDX1 were positively correlated with the expression of autophagy marker genes Atg5, Atg12, and BECN-1. This evidence suggests that there may be some interaction between FDX1 mediated Cuproptosis and autophagy. In summary, FDX1 may serve as a potential immunotherapy target and prognostic marker for Glioma.

Identification of a new gene signature for prognostic evaluation in cervical cancer: based on cuproptosis-associated angiogenesis and multi-omics analysis

“…Cell-cell communication analysis based on single-cell sequencing helps to reveal the tumor immune microenvironment and changes in the tumor itself [ 51 ]. Previous studies have shown that FDX1 , as a key gene in cuproptosis, is involved in the progression of hepatocellular carcinoma [ 52 ] and glioma [ 53 ] as well as tumor immunity and drug sensitivity [ 54 ]. To investigate the relationship between angiogenesis and cuproptosis in cervical cancer, we identified two types of cells, FDX1 + tumor/epithelial cells and VEGFA + tumor/epithelial cells, and conducted cell-cell communication analysis.…”

A novel cuproptosis‐related prognostic gene signature in adrenocortical carcinoma

“…17 FDX1 serves as a regulator of protein lipoylation, mediating cuproptosis, 10 and is intricately linked to the cellular function, immune response, and disease prognosis of tumors. 18,19 It encodes a reductase that is known for reducing Cu 2+ to its more toxic form, Cu 1+ , 10 and exhibits differential expression and modification levels across various tumors. 19 A comprehensive multi-omics pan-cancer study conducted by Xu et al discovered that FDX1 is highly expressed in 15 types of tumors and exhibits low expression in 11 tumor types.…”

“…FDX1, a member of the [2Fe‐2S] cluster‐containing ferredoxin family, encodes a small iron–sulfur protein that is integral to the reduction of mitochondrial cytochromes and the synthesis of various steroid hormones 17 . FDX1 serves as a regulator of protein lipoylation, mediating cuproptosis, 10 and is intricately linked to the cellular function, immune response, and disease prognosis of tumors 18,19 . It encodes a reductase that is known for reducing Cu 2+ to its more toxic form, Cu 1+ , 10 and exhibits differential expression and modification levels across various tumors 19 .…”

The Molecular Mechanisms of Cuproptosis and Small-Molecule Drug Design in Diabetes Mellitus

“…FDX1 is a protein involved in cuproptosis localized to the mitochondrial membrane [ 50 ]. Recent studies have identified FDX1 as a regulator of protein lipoylation involved in cellular cuproptosis [ 51 , 52 ]. Additionally, studies have identified FDX1 as a direct target of ES which enhances a distinct form of Cu-dependent cell death [ 53 ].…”