Expression and prognostic significance of CRKL in clear cell renal cell carcinoma

Clear cell renal cell carcinoma (ccRCC) is an aggressive kidney malignancy with limited prognostic biomarkers. CRKL has been implicated in cancer progression, but its prognostic value and immune associations in ccRCC remain unclear. Using TCGA, GEO, and UALCAN databases, we analyzed CRKL expression. Kaplan-Meier and multivariate Cox regression assessed survival; TIMER and TISIDB evaluated immune infiltration; LinkedOmics databases and GSEA identified enriched pathways. CRKL was significantly overexpressed in ccRCC tissues at both mRNA and protein levels. Surprisingly, high CRKL expression was associated with better overall survival (OS), disease-specific survival (DSS), progression-free interval (PFI), and disease free survival (DFS). Multivariate Cox analysis identified CRKL as an independent favorable prognostic factor (OS: HR = 0.469, 95% CI: 0.302-0.729, P < 0.001). CRKL positively correlated with immune cell infiltration and immune-related pathways. In conclusion, CRKL is overexpressed in ccRCC, paradoxically, higher expression predicts better prognosis and is associated with immune-active tumor microenvironment features. These findings suggest that the favorable prognosis associated with CRKL may be attributable to its immunomodulatory role within the tumor microenvironment, highlighting its potential as a novel prognostic biomarker for ccRCC.