Abstract
OBJECTIVES: Clear cell renal cell carcinoma (ccRCC) may later metastasize despite curative surgery. This study asked whether transcriptomic alterations detectable at nephrectomy are associated with subsequent metastatic progression, and whether such signals retain prognostic relevance in overt metastatic disease. METHODS: Bulk RNA sequencing was performed in 30 ccRCC patients without metastasis at surgery; 4 developed distant metastasis during follow-up. Differential expression, enrichment, and network analyses identified hub genes, which were screened by ROC analysis with bootstrap optimism correction. External validation used TCGA-KIRC focusing on patients metastatic at baseline (M1) to evaluate overall and disease-specific survival with multivariable Cox models (per-SD expression, adjusted for age, sex, and stage); Kaplan-Meier curves were shown for visualization only. RESULTS: Fifty-nine DEGs distinguished patients who later metastasized from those who remained metastasis-free, with enrichment in mitotic and chromosomal-segregation pathways. Five hub genes (BASP1, CDCA8, KIF2C, LMNB1, TROAP) showed high discrimination in the discovery set (optimism-corrected AUC ~0.92-0.93). In TCGA-M1, CDCA8, and TROAP were consistently associated with worse survival and remained significant in multivariable models. CONCLUSIONS: Dysregulation of mitotic control may underlie latent metastatic competence in ccRCC. CDCA8 and TROAP emerge as candidate prognostic biomarkers, linking postoperative metastatic progression in an initially M0 cohort with survival in metastatic disease. These hypothesis-generating findings warrant validation in larger, prospective cohorts.