Abstract
To identify a robust panel of microRNA (miRNA) signatures that can distinguish renal cell carcinoma (RCC) from normal kidney using miRNA expression levels. We performed a comprehensive meta-analysis of 29 published studies that compared the miRNA expression profiles of RCC tissues and adjacent normal tissues (NT) to determine candidate miRNAs as prognostic biomarkers for RCC. Using vote-counting strategy and robust rank aggregation method, we identified a statistically significant miRNA meta-signature of two upregulated (miR-21, miR-210) and three downregulated (miR-141, miR-200c and miR-429) miRNAs. X-tile plot was used to generate the optimum cut-off point for the 15 different deregulated miRNAs and Kaplan-Meier method was used to calculate CSS. In a cohort of 45 patients, the high expression of miR-21 (HR: 5.46, 95%CI: 2.02-53.39) and miR-210 (HR: 6.85, 95%CI: 2.13-43.36), the low expression of miR-141 (HR: 0.16, 95%CI: 0.004-0.18), miR-200c (HR: 0.08, 95%CI: 0.01-0.43) and miR-429 (HR: 0.18, 95%CI: 0.02-0.50) were associated with poor cancer-specific survival (CSS) following RCC resection. We also constructed a five-miRNAs-based classifier as a reliable prognostic and predictive tool for CSS in patients with RCC, especially in clear cell RCC (ccRCC) (HR: 5.46, 95% CI: 1.51-19.66). This method might facilitate patient counselling and individualise management of RCC.
Highlights
To identify a robust panel of microRNA signatures that can distinguish renal cell carcinoma (RCC) from normal kidney using miRNA expression levels
542 different expressed miRNAs were reported in the 29 miRNA expression profiling datasets; 11 were up-regulated (Supporting Information Table 2) and 38 were down-regulated (Supporting Information Table 3) in at least three studies. 10 and 9 studies reported relative miR-210 and miR-21 upregulated expression fold change, respectively. 14, 12 and 8 studies consistently reported relative miR-141, miR200c and miR-429 downregulated expression fold change, respectively
The results showed that the expression levels of miR-21, miR-210, miR-122, miR-155 and miR-224 were increased, whereas the levels of miR138, miR-204, miR-218, miR-363, miR-532, miR-141, miR-200a, miR-200b, miR-200c and miR-429 were decreased in the RCC tissues compared with adjacent normal tissue
Summary
To identify a robust panel of microRNA (miRNA) signatures that can distinguish renal cell carcinoma (RCC) from normal kidney using miRNA expression levels. We constructed a five-miRNAs-based classifier as a reliable prognostic and predictive tool for CSS in patients with RCC, especially in clear cell RCC (ccRCC) (HR: 5.46, 95% CI: 1.51-19.66). Surgical resection is still the only definitive treatment for RCC, but after the curative nephrectomy, 20–40% patients will develop recurrence. We conducted an integrated miRNA expression profiling analysis which analysis datasets separately and aggregate the resulting miRNA lists This strategy has been applied to identify gene co-expression networks[35] and to define more robust sets of cancer-related genes[36] and miRNAs37,38
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