Abstract
Interferon regulatory factor 7 (IRF7) regulates immune responses but its prognostic role in kidney renal clear cell carcinoma (KIRC) is undefined. Given KIRC's high incidence (70-80% of renal cancers) and limited late-stage therapies, we assessed IRF7's clinical utility through multi-omics analysis. Using TCGA, GTEx, CPTAC, and tissue microarrays, we analyzed IRF7 in 33 cancers. Assessments included survival (DSS/PFI/OS), functional enrichment (GSEA), drug sensitivity (GSCA), single-cell functional state analysis using the CancerSEA database, and prognostic nomogram construction. IRF7 was dysregulated in 22 cancers (KIRC: p < 0.001), with elevated expression correlating to poor survival (p < 0.01). It associated with immune checkpoints, epigenetic modifiers, T-cell activity, and methylation. Functional analyses implicated IRF7 in fatty acid metabolism, oxidative phosphorylation, and drug sensitivity. A KIRC-specific nomogram predicted OS with high accuracy. Tissue microarrays confirmed IRF7 overexpression in KIRC versus normal tissues (p < 0.001), linked to reduced survival. IRF7 is a novel prognostic biomarker in KIRC, influencing tumor immunity and therapy response. Its integration into clinical nomograms could guide precision immunotherapy strategies.