Integrated Multi-Omics Analysis Uncovers SELENOP and TAF10 as Mechanistically Distinct Therapeutic Targets in ccRCC through Lactate Metabolism and EMT Regulation with Repurposing of Diosmin and Micafungin Sodium

Methods

We integrated scRNA-seq from three cohorts with TCGA/GEO bulk transcriptomic data, constructed a 15-gene LASSO prognostic risk model using differentially expressed genes, performed CRISPR-Cas9 functional studies in A498 and OS-RC-2 cells and xenograft models, and conducted structure-based virtual screening with molecular dynamics simulations to identify repurposable drugs targeting SELENOP and TAF10. Results: The 15-gene signature stratified patients by survival and immune landscape across multiple validation cohorts.

SELENOP suppressed BSG-mediated lactate export, whereas TAF10 drove SRGN-dependent EMT. Virtual screening identified Diosmin and Micafungin Sodium as SELENOP agonist and TAF10 antagonist, both showing anti-tumor efficacy preclinically with synergistic combination effects. Conclusions: SELENOP and TAF10 represent mechanistically distinct therapeutic targets via BSG–lactate and SRGN–EMT pathways, and Diosmin with Micafungin Sodium merit clinical investigation as ccRCC repurposed therapeutics.