Detection of let-7 miRNAs in urine supernatant as potential diagnostic approach in non-metastatic clear-cell renal cell carcinoma

Abstract

IntroductionUrinary microRNAs (miRNAs) are emerging as a clinically useful tool for early and non-invasive detection of various types of cancer. The aim of this study was to evaluate whether let-7 family miRNAs differ in their urinary concentrations between renal cell carcinoma (RCC) cases and healthy controls.Materials and methodsIn the case-control study, 69 non-metastatic clear-cell RCC patients and 36 gender/age-matched healthy controls were prospectively enrolled. Total RNA was purified from cell-free supernatant of the 105 first morning urine specimens. Let-7 family miRNAs were determined in cell-free supernatant using quantitative miRNA real-time reverse-transcription PCR and absolute quantification approach.ResultsConcentrations of all let-7 miRNAs (let-7a, let-7b, let-7c, let-7d, let-7e and let-7g) were significantly higher in urine samples obtained from RCC patients compared to healthy controls (P < 0.001; P < 0.001; P = 0.005; P = 0.006; P = 0.015 and P = 0.002, respectively). Subsequent ROC analysis has shown that let-7a concentration possesses good ability to differentiate between cases and controls with area under curve being 0.8307 (sensitivity 71%, specificity 81%).ConclusionsWe have shown that let-7 miRNAs are abundant in the urine samples of patients with clear-cell RCC, and out of six let-7 family members, let-7a outperforms the others and presents promising non-invasive biomarker for the detection of RCC.

Genome‐wide identification of urinary cell‐free microRNAs for non‐invasive detection of bladder cancer

“…Urinary cell-free miRNAs are emerging as potential biomarkers of urologic cancers [7]. In our previous study, we have shown that cell-free miRNAs are abundant in urine of renal cell carcinoma patients and present promising non-invasive biomarkers [9]. Similarly, several reports described specific miRNA expression profiles in urine of patients with BCA indicating their potential usage for early detection of the disease, prognosis prediction or therapy response [10][11][12].…”

Circulating microRNAs as potential cancer biomarkers: the advantage and disadvantage

“…Several miRNAs including miR-210-3p were upregulated in urine from transitional cell carcinoma patients and capable to facilitate cancer diagnosis [ 69 ]. All members of let-7 families were significantly elevated in urine from clear-cell renal cell cancer (ccRCC) patients [ 70 ], while a combination of urinary exosomal miR-34b-5p, miR-126-3p, and miR-449a-3p could be favorable for ccRCC diagnosis [ 71 ]. A panel of four breast cancer-related miRNAs (miR-21-5p, miR-125b-5p, miR-155-5p, and miR-451-5p) was also differentially expressed in urine samples of breast cancer patients and exhibited their diagnostic value [ 72 ].…”

MicroRNAs as Urinary Biomarker for Oncocytoma

“…Besides the studies from our group using urine for the detection of RCCs by high levels of miR-15a [ 19 ], there are only two other reports in renal cancer using the urine as material for a liquid biopsy. Fedorko et al [ 71 ] detected let-7 miRs in urine supernatant as a potential diagnostic approach in nonmetastatic clear cell renal cell carcinoma. A second study by Butz et al [ 72 ] screened urinary miRs for differential diagnosis between patients with renal tumors (malignant and benign) and controls.…”