Prognostic and immunological role of FDX1 in pan-cancer: an in-silico analysis

Sci Rep. 2023 May 16;13(1):7926. doi: 10.1038/s41598-023-34752-1.

Abstract

Previous research has demonstrated that ferredoxin 1 (FDX1) contributes to the accumulation of toxic lipoylated dihydrolipoamide S-acetyltransferase (DLAT) and results in cuproptotic cell death. However, the role that FDX1 plays in human cancer prognosis and immunology is still not well understood. The original data was obtained from TCGA and GEO databases and integrated using R 4.1.0. The TIMER2.0, GEPIA, and BioGPS databases were used to explore FDX1 expression. The impact of FDX1 on prognosis was analyzed using the GEPIA and Kaplan-Meier Plotter databases. External validation will be performed using the PrognoScan database. FDX1 expression in different immune and molecular subtypes of human cancers was evaluated using the TISIDB database. The correlation between FDX1 expression and immune checkpoints (ICP), microsatellite instability (MSI), and tumor mutational burden (TMB) in human cancers was analyzed using R 4.1.0. The TIMER2.0 and GEPIA databases were used to study the relationship between FDX1 expression and tumor-infiltrating immune cells. With the c-BioPortal database, we investigated the genomic alterations of FDX1. Pathway analysis and assessment of the sensitivity potential of FDX1-related drugs were also performed. Using the UALCAN database, we analyzed the differential expression of FDX1 in KIRC (kidney renal clear cell carcinoma) with different clinical features. Coexpression networks of FDX1 were analyzed using LinkedOmics. In general, FDX1 was expressed differently in different types of cancer in humans. Expression of FDX1 was strongly correlated with patient prognosis, ICP, MSI, and TMB. FDX1 was also participated in immune regulation and the tumor microenvironment. Coexpression networks of FDX1 were primarily involved in oxidative phosphorylation regulation. Pathway analysis revealed that the expression of FDX1 was correlated to cancer-related and immune-related pathways. FDX1 has the potential to serve as a biomarker for pan-cancer prognosis and immunology, as well as a novel target for tumor therapy.

MeSH terms

  • Carcinoma, Renal Cell* / genetics
  • Cell Death
  • Humans
  • Kidney Neoplasms* / genetics
  • Microsatellite Instability
  • Oxidative Phosphorylation
  • Prognosis
  • Tumor Microenvironment / genetics