Clinicopathological significance and prognostic value of the MSI1/MTFR2 axis in clear cell renal cell carcinoma: linking stemness and mitochondrial dynamics.

Clear cell renal cell carcinoma (ccRCC) carries a high risk of recurrence, necessitating reliable prognostic biomarkers. This study evaluated the immunohistochemical expression, clinicopathological significance, and prognostic value of Musashi-1 (MSI1) and MTFR2 in ccRCC. Expression of MSI1 and MTFR2 was evaluated by immunohistochemistry in 124 ccRCC cases and paired non-neoplastic renal tissues. Associations with clinicopathological parameters and prognostic scoring models (SSIGN, UISS, SIS) were assessed, applying False Discovery Rate (FDR) procedures for multiple hypothesis testing. Progression-free survival (PFS) and disease-free survival (DFS) were analyzed using Kaplan-Meier curves, log-rank tests, and multivariate Cox regression models with multicollinearity diagnostics (VIF). Both MSI1 and MTFR2 were significantly upregulated in ccRCC compared to normal tissues (p < 0.001) and positively correlated with each other (r = 0.676, p < 0.001). High expression of either marker was significantly associated with adverse baseline features (larger tumour size, higher WHO/ISUP grade, advanced T-stage; q < 0.05) and higher-risk SSIGN, UISS, and SIS scores. Elevated MSI1 and MTFR2 predicted significantly shorter PFS and DFS (p < 0.001). Multivariate analysis confirmed T-stage, WHO/ISUP grade, MSI1, and MTFR2 as independent prognostic factors for PFS and DFS. The MSI1/MTFR2 axis represents strong independent prognostic signature in ccRCC and may enhance risk stratification while highlighting potential therapeutic targets.