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Comparative Study
, 116 (1), 77-84

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

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.


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.


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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