AUTHOR=Wang Tao , Liu Yufeng , Li Qing , Luo Yang , Liu Dawei , Li Bin 

TITLE=Cuproptosis-related gene FDX1 expression correlates with the prognosis and tumor immune microenvironment in clear cell renal cell carcinoma

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.999823

DOI=10.3389/fimmu.2022.999823

ISSN=1664-3224

ABSTRACT=<sec><title>Background</title><p>Cuproptosis, a newly discovered form of cell death, is regulated by protein lipoylation and is related to mitochondrial metabolism. However, further research is needed to determine how the cuproptosis-related gene ferredoxin 1 (<italic>FDX1</italic>) affects the tumor immune response and its prognostic significance in clear cell renal cell carcinoma (ccRCC).</p></sec><sec><title>Methods</title><p>The Cancer Genome Atlas was used to screen for <italic>FDX1</italic> gene expression in ccRCC and healthy tissue samples. The results were validated using the Gene Expression Omnibus and the Human Protein Atlas. Multivariable analysis and Kaplan-Meier survival curves were used to examine the relationship between <italic>FDX1</italic> gene expression, clinicopathological parameters, and overall survival (OS). The protein network containing <italic>FDX1</italic> gene interaction was constructed using the online Search Tool for the Retrieval of Interacting Genes/Proteins. The relationship between <italic>FDX1</italic> gene expression and immune cell infiltration in ccRCC was examined using Gene Ontology, gene set enrichment analysis (GSEA), and a single-sample GSEA. Using the Gene Expression Profiling Interactive Analysis and Tumor Immune Estimation Resource databases, we investigated the relationship between <italic>FDX1</italic> gene expression, the degree of immune cell infiltration, and the corresponding gene marker sets.</p></sec><sec><title>Results</title><p>ccRCC samples had significantly (p &lt; 0.05) lower <italic>FDX1</italic> gene expression levels than normal tissue samples. Lower <italic>FDX1</italic> gene expression levels were strongly associated with higher cancer grades and more advanced tumor–node–metastasis stages. The findings of multivariate and univariate analyses illustrated that the OS in ccRCC patients with low FDX1 expression is shorter than in patients with high FDX1 expression (p &lt; 0.05). Ferredoxin reductase and CYP11A1 are key proteins interacting with the <italic>FDX1</italic> gene, and ccRCC with an FDX1 enzyme defect was associated with a low number of invading immune cells and their corresponding marker.</p></sec><sec><title>Conclusion</title><p>In ccRCC, decreased FDX1 expression was linked to disease progression, an unfavorable prognosis, and dysregulated immune cell infiltration.</p></sec>