Integrative Analysis of GEO Datasets and Mendelian Randomization Reveals a Potential Role ofISOC1 in Renal Cell...

Background: Renal cell carcinoma (RCC) is a leading malignancy of the urinary system, with clear cell RCC (ccRCC) being the most prevalent subtype. Despite advances in treatment, the prognosis of advanced RCC remains poor, and the molecular mechanisms underlying its pathogenesis are not fully understood. Methods: This study utilized multiple renal cancer cohorts from the Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs). By integrating Mendelian randomization (MR) analyses of expression quantitative trait loci (eQTL) and protein quantitative trait loci (pQTL), we investigated causal associations between candidate genes and RCC. Immune infiltration, drug sensitivity, and survival analyses were performed to further explore functional significance. In vitro experiments validated the biological role ofISOC1 in RCC progression. Results: We focused on ISOC1, a gene previously implicated in other malignancies but not well studied in RCC. Through integrative MR analysis, we identified ISOC1 as a novel RCC-associated gene, with potential tumor-suppressive functions in this specific context. ISOC1 expression was significantly linked to tumor immune infiltration, drug sensitivity, and patient prognosis. Functional assays demonstrated that ISOC1 knockdown promoted RCC cell proliferation, migration, and invasion. Conclusions: ISOC1 plays a critical role in RCC progression and may act as a tumor suppressor. These findings highlight ISOC1 as a potential biomarker for prognosis and a promising target for therapeutic intervention in RCC. Moreover, this study underscores the utility of MR-based integrative analyses in uncovering novel molecular mechanisms and therapeutic targets for cancer.