Int J Med Sci 2017; 14(1):53-57. doi:10.7150/ijms.17027
Polymorphisms in MicroRNA Binding Sites Predict Colorectal Cancer Survival
1. Department of Pharmacy, Zhongxiao Branch, Taipei City Hospital, Taipei, Taiwan.
2. Department of Colorectal Surgery, China Medical University Hospital, Taichung, Taiwan.
3. Division of Colorectal Surgery, Department of Surgery, Chung Shan Medical University Hospital, Taichung, Taiwan.
4. Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
5. Department of Obstetrics and Gynecology, China Medical University Hospital, Taichung, Taiwan.
6. Department of Pharmacy, China Medical University, Taichung, Taiwan.
7. Sex Hormone Research Center, China Medical University Hospital, Taichung, Taiwan.
8. Department of Nursing, Asia University, Taichung, Taiwan.
Background: MicroRNAs (miRNAs) mediate negative regulation of target genes through base pairing, and aberrant miRNA expression has been described in cancers. We hypothesized that single nucleotide polymorphisms (SNPs) within miRNA target sites might influence clinical outcomes in patients with colorectal cancer.
Methods: Sixteen common SNPs within miRNA target sites were identified, and the association between these SNPs and overall survival was assessed in colorectal cancer patients using Kaplan-Meier analysis, Cox regression model, and survival tree analysis.
Results: Survival tree analysis identified a higher-order genetic interaction profile consisting of the RPS6KB1 rs1051424 and ZNF839 rs11704 that was significantly associated with overall survival. The 5-year survival rates were 74.6%, 62.7%, and 57.1% for the low-, medium-, and high-risk genetic profiles, respectively (P = 0.006). The genetic interaction profile remained significant even after adjusting for potential risk factors. Additional in silico analysis provided evidence that rs1051424 and rs11704 affect RPS6KB1 and ZNF839 expressions, which in turn is significantly correlated with prognosis in colorectal cancer.
Conclusion: Our results suggest that the genetic interaction profiles among SNPs within miRNA target sites might be prognostic markers for colorectal cancer survival.
Keywords: colorectal cancer, survival, microRNAs, single nucleotide polymorphism, genetic interaction.
Yang YP, Ting WC, Chen LM, Lu TL, Bao BY. Polymorphisms in MicroRNA Binding Sites Predict Colorectal Cancer Survival. Int J Med Sci 2017; 14(1):53-57. doi:10.7150/ijms.17027. Available from http://www.medsci.org/v14p0053.htm