# Liquid Biopsy in Clear Cell Renal Cell Carcinoma: Diagnostic Potential of Urinary miRNAs

## TL;DR

This study explores the potential of urinary microRNAs as non-invasive biomarkers for diagnosing and monitoring clear cell kidney cancer.

## Contribution

The study identifies specific urinary miRNAs that decrease after tumor removal, suggesting their utility in monitoring treatment response.

## Key findings

- Levels of miR-15a, miR-16, and miR-210 significantly decreased after tumor removal, indicating their link to cancer presence.
- Urinary miRNA profiles partially normalized one month after surgery, showing potential for postoperative monitoring.
- Some miRNAs correlated with clinical parameters like age and surgical time, supporting their biological relevance.

## Abstract

Clear cell renal cell carcinoma is the most common form of kidney cancer and is often discovered incidentally because early disease rarely causes symptoms. This creates an urgent need for non-invasive biomarkers that can help in tumour detection and monitor patients after surgery. MicroRNAs in urine are promising candidates because they are stable and reflect tumour activity. In this study, we measured five urinary microRNAs in urine of patients before surgery, shortly after surgery, and one month later, and compared the results with those from healthy individuals. Several microRNAs decreased after tumour removal, suggesting that their levels are closely related to the presence of cancer. Some microRNAs were also associated with clinical features, supporting their biological relevance. These findings indicate that urinary microRNAs may serve as useful, minimally invasive biomarkers for diagnosing clear cell renal cell carcinoma and for monitoring patients after treatment.

Background: Clear cell renal cell carcinoma (ccRCC) is the most prevalent kidney cancer subtype and, in most cases, it is incidentally diagnosed, as early-stage disease is often asymptomatic. Therefore, the identification of stable, noninvasive biomarkers is a major unmet clinical need. Urinary microRNAs (miRNAs) have emerged as promising candidates since they are extraordinarily stable in urine and show a close relationship with tumour biology. Methods: In this study, urinary expression levels of five miRNAs (miR-15a, miR-15b, miR-16, miR-210, and miR-let-7b) were analysed in RCC patients before surgery, 5 days after, and one month after surgery, and compared to healthy controls. Results: Non-parametric analyses revealed significant postoperative decreases for miR-15a (p = 0.002), miR-16 (p = 0.025), miR-210 (p = 0.030), and in the overall miRNA Sum (p = 0.002), suggesting that these miRNAs are directly linked to tumour presence. In the comparison between preoperative and one-month postoperative samples, miR-let-7b (p = 0.049) and the global miRNA Sum (p = 0.037) remained significantly reduced after intervention, indicating a partial normalisation of urinary miRNA profiles. Correlation analyses demonstrated positive associations between specific miRNAs and clinical parameters such as age, ischemia time, and surgical time, reinforcing their potential relevance to tumour biology and treatment response. Conclusions: These findings support urinary miRNAs as promising, minimally invasive biomarkers for ccRCC diagnosis and postoperative monitoring.