Role of MicroRNA-21 and MicroRNA-210 Expression in the Diagnosis, Prognosis, and Metastatic Potential of Renal Cell Carcinoma Subtypes

Background and Objectives: Differentiating between subtypes of renal cell carcinoma (RCC) can be challenging due to overlapping immunohistochemical and histomorphological features. Furthermore, despite the evaluation of numerous histopathologic parameters, predicting metastasis and prognosis remains unclear. In this study, we aimed to evaluate the potential of microRNA (miRNA) expression levels in establishing definitive diagnoses, assessing metastatic potential, and determining patient prognosis. Materials and Methods: A total of 35 clear cell RCC (cc-RCC), 11 chromophobe RCC (ch-RCC), 9 papillary RCC (p-RCC) cases, and 9 cc-RCC metastases were retrospectively analyzed. MiRNA-21 and miRNA-210 expression profiles were assessed using non-parametric tests, receiver operating characteristic (ROC) analysis, and Cox regression models. Results: The expression levels of both miRNA-21 and miRNA-210 were significantly elevated in cc-RCC and p-RCC cases. In contrast, miRNA-210 expression levels were significantly reduced in all ch-RCC cases, whereas miRNA-21 expression showed no significant change. Although miRNA-21 expression levels were higher in metastases compared to primary cc-RCC tumors, the difference was not statistically significant (p=0.053). No significant difference was observed in miRNA-210 expression between metastatic and primary cc-RCC tumors (p=0.237). Regardless of histological subtype, an increase in miRNA-210 expression was associated with a significant reduction in overall survival (p=0.03, HR=1.729, 95% CI: 1.043-2.864). Conclusion: The findings suggest that miRNA-21 and miRNA-210 expression levels can help distinguish ch-RCC from cc-RCC and p-RCC. Additionally, miRNA-210, but not miRNA-21, may differentiate cc-RCC from p-RCC. Higher miRNA-210 expression levels were associated with worse overall survival in RCC patients. While miRNA-21 levels were increased in cc-RCC metastases, further studies with larger sample sizes are needed to establish its role in predicting metastasis.