# The miR-21-5p, miR-30c-5p, and miR-182-5p as Biomarkers in Clear Cell Renal Cell Carcinoma: A Southeastern Romanian Cohort Study

## TL;DR

This study identifies three microRNAs as potential non-invasive biomarkers for diagnosing and predicting outcomes in kidney cancer patients from southeast Romania.

## Contribution

The study evaluates miR-21-5p, miR-30c-5p, and miR-182-5p as novel non-invasive biomarkers for clear cell renal cell carcinoma in a specific regional cohort.

## Key findings

- miR-21-5p and miR-182-5p were overexpressed, while miR-30c-5p was downregulated in tumor tissues and serum exosomes.
- miR-182-5p and miR-21-5p levels correlated with tumor localization and lymph node involvement.
- Combined miRNA panels showed high diagnostic accuracy (AUC = 0.94 in tissue, AUC = 0.93 in exosomes).

## Abstract

Background: This study aimed to evaluate the expression and clinical relevance of three mature miRNAs (miR-21-5p, miR-30c-5p, and miR-182-5p) in patients with clear cell renal cell carcinoma (ccRCC) from southeast Romania, and to explore their potential as non-invasive diagnostic and prognostic biomarkers. Methods: miRNA expression levels were measured using TaqMan® MGB and qRT-PCR in paired tumor and adjacent non-cancerous tissues, as well as in serum-derived exosomes, from 26 ccRCC patients. Statistical analysis included the Wilcoxon test for group comparisons and non-parametric tests for correlations with clinicopathological features. Receiver operating characteristic (ROC) curves were used to assess diagnostic performance, and miRNA panels were constructed for improved accuracy. Results: Significant dysregulation of the investigated miRNAs was observed. miR-21-5p was markedly overexpressed in both tumor tissues (3.46-fold, p < 0.001) and serum exosomes (3.26-fold, p < 0.001). miR-182-5p showed modest overexpression in tissues (0.56-fold, p < 0.001) and serum (0.85-fold, p < 0.001), whereas miR-30c-5p was significantly downregulated in both tissues (2.48-fold decrease, p < 0.001) and serum exosomes (2.29-fold decrease, p = 0.0003). Elevated miR-182-5p expression correlated with tumor localization in the right kidney (p = 0.02) and lymph node involvement (p = 0.04). Similarly, higher miR-21-5p levels in serum exosomes were associated with right-sided tumors (p = 0.01). ROC analysis revealed distinct expression profiles for all three miRNAs between ccRCC and normal tissue, both in tissue and exosomal samples (all p < 0.05). Combined biomarker panels yielded high diagnostic performance (AUC = 0.94 for tissue, AUC = 0.93 for exosomes). Conclusions: This study underscores the potential of miR-21-5p, miR-30c-5p, and miR-182-5p as non-invasive biomarkers for ccRCC diagnosis and prognosis. The use of serum exosomal miRNA panels offers a promising alternative to tissue-based diagnostics in Romanian ccRCC patients.