MicroRNA profile in stage I clear cell renal cell carcinoma predicts progression to metastatic disease

Objective: This study sought to identify microRNA (miRNA) profiles of small, pathologically confirmed stage 1 clear cell renal cell carcinoma (ccRCC) tumors that are associated with progression to metachronous metastatic disease. Materials and methods: Fifty-five pathologic stage 1 ccRCC tumors ≤5cm, from 2 institutions, were examined in a miRNA screening, followed by a validation study. For the screening phase 752 miRNA were evaluated on each sample to identify those with differential expression between tumors that subsequently did (n = 10) or did not (n = 10) progress to metastatic disease. For the validation, 35 additional samples (20 nonprogressors and 15 with distant progression) were utilized to investigate 20 miRNA to determine if a miRNA panel could differentiate aggressive tumors: associations of miRNA expression with cancer specific survival was also investigated. Results: In the screening analysis, 35 miRNA were differentially expressed (P < 0.05, FDR < 0.1) between the groups. In the validation, 11 miRNA were confirmed to have differential expression. The miRNA -10a-5p, -23b-3p, and -26a-5p differentiated nonprogressive and distant progressive disease with a sensitivity of 73.3% and a specificity of 85% (AUC=0.893). In addition, levels of miR-30a-3p and -145-5p were identified as independent prognostic factors of cancer specific survival. Conclusions: This investigation identified miRNA biomarkers that may differentiate between non-progressive ccRCC tumors and those that progress to metastatic disease in this group of stage I tumors. The miRNA profiles determined in this study have the potential to identify patients with small renal masses who are likely to have progressive ccRCC. Such information may be valuable to incorporate into predictive models.