Identification of FMR1 as a novel cancer prognostic and immunotherapy biomarker through renal cancer experimental validation and pan-cancer analysis

BACKGROUND: FMR1, a gene classically linked to Fragile X syndrome, functions as a multifunctional RNA-binding protein regulating RNA metabolism. Emerging evidence indicates its role in modulating cancer progression and tumor immunity, yet a comprehensive pan-cancer analysis to confirm its viability as a biomarker for cancer screening, prognosis, and precision therapy remains lacking. METHODS: We first validated FMR1 expression in renal cell carcinoma cell lines via qRT-PCR and assessed its functional role using colony-formation, wound-healing, and Transwell assays. Subsequently, we performed pan-cancer analyses by mining multi-omic data from public databases including UCSC Xena, TCGA, GTEx, TIMER, and TISIDB, integrating expression, prognosis, immune infiltration, and genetic alteration data. RESULTS: FMR1 was downregulated in renal cancer cell lines, and its overexpression inhibited cell proliferation and migration. Pan-cancer analysis revealed dysregulated FMR1 expression across multiple tumors. Low FMR1 expression correlated with poor prognosis in cancers like KIRC and SKCM. It also correlated with RNA methylation genes, immune/molecular subtypes, immune checkpoint genes, and immune cell infiltration. FMR1 amplification was the most frequent genetic alteration, and it demonstrated possibly improved predictive value compared to some traditional biomarkers. CONCLUSION: FMR1 acts as a tumor suppressor in renal cancer and represents a promising pan-cancer biomarker for screening, prognostic evaluation, and immunotherapy response prediction, providing new insights for precision cancer therapy.