MicroRNAs as prognostic molecular signatures in renal cell carcinoma: a systematic review and meta-analysis

Abstract

This is a systematic review of studies investigating the prognostic value of different microRNAs (miRs) in renal cell carcinoma (RCC). Twenty-seven relevant studies were identified, with a total of 2578 subjects. We found that elevated expression of miR-21, miR-1260b, miR-210, miR-100, miR-125b, miR-221, miR-630, and miR-497 was associated with a poor prognosis in RCC patients. Conversely, decreased expression of miR-106b, miR-99a, miR-1826, miR-215, miR-217, miR-187, miR-129-3p, miR-23b, miR-27b, and miR-126 was associated with a worse prognosis. We performed meta-analyses on studies to address the prognostic value of miR-21, miR-126, miR-210, and miR-221. This revealed that elevated miR-21 expression was associated with shorter overall survival (OS; hazard ratio [HR], 2.29; 95% confidence interval [CI], 1.28-4.08), cancer specific survival (CSS; HR, 4.16; 95% CI, 2.49-6.95), and disease free survival (DFS; HR, 2.15; 95% CI, 1.16-3.98). The decreased expression of miR-126 was associated with shorter CSS (HR, 0.35; 95% CI, 0.15-0.85), OS (HR, 0.45; 95% CI, 0.30-0.69), and DFS (HR 0.30; 95% CI, 0.18-0.50). Our comprehensive systematic review reveals that miRs, especially miR-21 and miR-126, could be promising prognostic markers and useful therapeutic targets in RCC.

Keywords: meta-analysis; microRNA; prognosis biomarker; renal cell carcinoma; survival.

Figure 1. Flowchart of selecting studies for inclusion

Figure 2. Hazard ratios (HR) of miRs

The point estimate is bounded by a 95% confidence interval (CI), and the perpendicular line represents no increased risk for the outcome. OS = overall survival; CSS = cancer specific survival; DFS = disease free survival; RFS = recurrence free survival.

Figure 3. Forest plots of studies evaluating hazard ratios of aberrant miR-21 and mir-126 expression

A. miR-21, OS, CSS, DFS; B. miR-126, CSS, OS, DFS. OS = overall survival; CSS = cancer specific survival; DFS = disease free survival; HR = hazard ratio.

Figure 4. Forest plots of studies evaluating hazard ratios of aberrant miR-210 and mir-221 expression

A. miR-210, OS, CSS, DFS, RFS; B. miR-221, CSS, OS. OS = overall survival; CSS = cancer specific survival; DFS = disease free survival; RFS = recurrence free survival; HR = hazard ratio.