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Comparative Study
. 2017 Jan 3;116(1):77-84.
doi: 10.1038/bjc.2016.392. Epub 2016 Dec 1.

MicroRNA Profiling in Clear Cell Renal Cell Carcinoma Tissues Potentially Links Tumorigenesis and Recurrence With Obesity

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Free PMC article
Comparative Study

MicroRNA Profiling in Clear Cell Renal Cell Carcinoma Tissues Potentially Links Tumorigenesis and Recurrence With Obesity

X Shu et al. Br J Cancer. .
Free PMC article

Abstract

Background: Twenty to 40% localised RCC patients may experience recurrence after curative surgery. Limited miRNA predictors have been identified for ccRCC recurrence.

Methods: Through a multi-phase study design, we analysed miRNAs in tissues obtained from 203 ccRCC patients. Paired t-test was used for tumour-normal comparisons and Cox regression model was performed to compute hazard ratios (HRs) and corresponding 95% CIs.

Results: A 17-miRNA signature was identified that can concordantly classify >95% of tumour/adjacent normal samples. Significant enrichment was found as 6 out of 17 miRNAs were associated with obesity (binomial probability=0.001). Decreased levels of miR-204-5p and miR-139-5p were each associated with an approximately three-fold increased risk of recurrence (P<0.01). Risk score was generated based on expressions of miR-204-5p and miR-139-5p, and the trend test was significant in both discovery and validation sets (Pfor trend<0.05). Striking MST reduction was observed for patients with a high-risk score (high vs low: discovery, 9.4 vs >97.7 months; validation, 20.8 vs >70.3 months). Expressions of miR-204-5p were also associated with body mass index (β=5.64, P<0.001). Significant inverse correlations were observed and validated between miR-204-5p and 13 obesity-related genes (r<0, P<0.01).

Conclusions: We identified 17 miRNAs dysregulated in ccRCC tissues and showed that low expressions of miR-204-5p and miR-139-5p were associated with the higher risk of recurrence. The link between miR-204-5p and ccRCC recurrence may be partially mediated by regulating the expression of targeted obesity-related genes.

Figures

Figure 1
Figure 1
Study flowchart.
Figure 2
Figure 2
Heatmap for MDACC discovery set of miRNA tumour–normal comparisons. A full colour version of this figure is available at British Journal of Cancer online.
Figure 3
Figure 3
Five-year recurrence-free survival curves for miR-204-5p and miR-139-5p. (A, B) Kaplan–Meier curves of miR-204-5p in the discovery/validation. (C, D) Kaplan–Meier curves of miR-139-5p in the discovery/validation.

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