MicroRNAs in Serum Exosomes as Potential Biomarkers in Clear-cell Renal Cell Carcinoma

Abstract

Background: Circulating microRNAs (miRNAs) in exosomes are emerging as clinically useful tools for cancer detection. However, little is known about their diagnostic impact in clear-cell renal cell carcinoma (ccRCC).

Objective: To investigate whether miRNAs in serum exosomes can serve as biomarkers in ccRCC.

Design, setting, and participants: Serum samples were obtained from 82 patients with ccRCC and 80 healthy volunteers. Exosomes were extracted and purified to selectively capture exosomes positive for tumor-associated epithelial cell adhesion molecule (EpCAM) via a magnetic bead technique. Total RNA was extracted and expression levels of miR-210, miR-1233, and miR-15a miRNAs were quantified and normalized to U6 levels.

Outcome measurements and statistical analysis: Expression levels were compared using a Mann-Whitney U-test, Friedman test, or Wilcoxon test. Receiver operating characteristic (ROC) curves were plotted to assess the diagnostic value of exosomal miRNAs for differentiation between ccRCC patients and controls.

Results and limitations: Expression levels of exosomal miR-210 and miR-1233 were significantly higher in ccRCC patients than in healthy individuals (both p<0.01). No significant difference was observed for exosomal miR-15a. Exosomal miR-210 and miR-1233 expression levels in different TNM stages were significantly higher than in the controls (all p<0.01). Exosomal miR-210 and miR-1233 expression levels were significantly lower in postoperative than in preoperative samples (both p<0.01). ROC analysis demonstrated that exosomal expression levels distinguished ccRCC patients from healthy individuals with 70% sensitivity and 62.2% specificity for miR-210, and 81% sensitivity and 76% specificity for miR-1233. The retrospective design and lack of other tumor subtypes are limitations of the study.

Conclusions: Serum exosomal miRNAs might represent potential diagnostic biomarkers in ccRCC in the future.

Patient summary: Circulating levels of exosomal microRNAs miR-210 and miR-1233 have potential as biomarkers for diagnostic and monitoring purposes in renal cancer in the future. These molecules can be measured in serum in so-called liquid biopsy.

Keywords: Biomarker; Clear-cell renal cell carcinoma; Exosome; Liquid biopsy; MicroRNA.