LIQUID BIOPSY IN CLEAR CELL RENAL CELL CARCINOMA: URINARY MIR-210-3P AS EMERGING SPECIFIC BIOMARKER
INTRODUCTION AND OBJECTIVE: The most common subtype of renal cell carcinoma (RCC) is clear cell RCC (ccRCC) that accounts for 70-80% of all renal malignancies. To date, no useful markers are available in clinical practice for early diagnosis and for optimal patient stratification. MicroRNAs, a class of small non-coding RNA, are emerging as promising molecules in the management of urological tumors suggesting the possibility of using them as non-invasive biomarkers. The aim of this study is to evaluate whether miR-210-3p may be an accurate non invasive diagnostic and prognostic biomarker for ccRCC patients.
METHODS: This study includes a cohort of 21 ccRCC cases underwent radical or partial nephrectomy. We analyzed by RTpPCR miR-210-3p levels in neoplastic and healthy tissues and in urine specimens collected at surgery and during follow-up visits (from 3 to 24 months) of all ccRCC cases, of which 18 disease-free patients and a small subgroup presenting metastatic progression. Urine samples were also collected from 16 healthy donors with similar demographic features. The specimens were frozen within 30 minutes from collection and stored at -80C until RNA extraction and microRNA expression analysis.
RESULTS: miR-210-3p was upregulated in ccRCC frozen tissues compared to matched normal counterparts. Next, we evidenced that miR-210-3p resulted significantly up-regulated in urine specimens collected from ccRCC patients at the time of surgery, compared to healthy samples. Of note, miR- 210-3p levels resulted significantly reduced in urine samples from disease-free patients during follow-up, compared to the baseline levels (time of surgery). In a small subgroup of patients presenting metastases, the urine levels of miR-210-3p increased and, interestingly, again decreased when responding to medical treatments.
CONCLUSIONS: This pilot study highlights the relevance of secreted miR-210-3p as powerful non invasive diagnostic and prognostic biomarker for ccRCC patients, with potential clinical applications from diagnosis to treatment.