Abstract
Abstract Obesity is an established risk factor for clear cell renal cell carcinoma (ccRCC) development and prognosis; however, the mechanisms underlying this link remain unclear. In the present study, we set to assess whether microRNAs (miRNAs) can serve as a molecular link between obesity and recurrence in ccRCC. Through bioinformatics tools and literature search, we identified 126 obesity-related miRNAs. Supplemented with 25 miRNAs which were differentially expressed between ccRCC from normal kidney, we tested the association of these miRNAs with ccRCC recurrence. Significantly decreased levels of hsa-miR-204-5p were found in recurrent ccRCC patients with an over 2-fold increased risk of recurrence (HR = 2.15, p = 0.028, MST = 25.6 vs. 47.2 months). Correlations between miRNA expression and the predicted target genes were tested using gene profiling data generated from these same patients. We found strong inverse correlations between miR-204 expression and several obesity-related genes, including IGF2BP2 (r = -0.40, p = 4.14×10−4), a member of the insulin growth receptor signaling pathway. This correlation was further validated in TCGA data (r = -0.58, p = 1.40×10−22). We also found that low level of hsa-miR-139-5p was significantly associated with increased recurrence risk (HR = 2.37, p = 0.026, MST = 32.2 vs. 51.3 months). In conclusion, we found a set of obesity-related miRNAs that are dysregulated in ccRCC tissues, and some of these miRNAs, such as hsa-miR-204-5p, were associated with the recurrence of RCC, potentially through regulating obesity-related gene expression. Citation Format: Xiang Shu, Michelle A. Hildebrandt, Jian Gu, Nizar M. Tannir, Surena Matin, Jose A. Karam. MicroRNA expression links obesity and recurrence in renal cell carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3999. doi:10.1158/1538-7445.AM2015-3999
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