Abstract
Background
Single nucleotide polymorphisms (SNPs) located in the 3′-UTR of miRNA target genes could affect miRNA-mediated gene regulation, thereby contributing to the susceptibility or prognosis of cancer. Accordingly, the present study analyzed SNPs located at putative miRNA-binding sites of the 3′-UTR of various genes and investigated their impact on the prognosis for patients with colorectal cancer.
Materials and methods
In total, 831 consecutive patients (discovery cohort, n = 309; validation cohort, n = 522) with curatively resected colorectal adenocarcinoma were enrolled. Plus, 157 SNPs were selected from an in silico analysis based on several miRNA and HapMap databases. The SNP genotyping was performed using a Sequenom MassARRAY. A luciferase assay was used to investigate whether miR-571 modulated PAUF gene expression when rs12373 was included in the PAUF 3′UTR region.
Results
In the discovery cohort, 18 SNPs were identified as possible prognostic biomarkers in a survival analysis. In the validation cohort, two SNPs (TPST1 rs3757417T>G and PAUF rs12373A>C) were significantly associated with prognosis in the same direction as the discovery cohort when adjusted for age, preoperative carcinoembryonic antigen level, and pathologic stage (discovery + validation cohort; TPST1 rs3757417T>G, disease-free survival (DFS), p value = 0.0004, overall survival (OS), p value = 0.01 in recessive model; PAUF rs12373A>C, DFS, p value = <0.0001, OS, p value = 0.0008 in dominant model). A significantly lower Renilla activity was observed in the rs12373 CC construct when compared with the rs12373 AA construct (p = 0.002).
Conclusion
The current study provides evidence that the TPST1 rs3757417T>G and PAUF rs12373A>C polymorphisms are possible prognostic biomarkers for patients with colorectal cancer.
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Acknowledgments
This work was supported in part by National Research Foundation (NRF) of Korea Grant funded by the Korean Government (NRF-2011-0015862) and in part by NRF funded by the Ministry of Education (2013R1A1A4A01008144).
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The authors declare no conflict of interest.
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Gyu Seog Choi and Hyo-Sung Jeon have contributed equally to this work.
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Kim, J.G., Chae, Y.S., Lee, S.J. et al. Genetic variation in microRNA-binding site and prognosis of patients with colorectal cancer. J Cancer Res Clin Oncol 141, 35–41 (2015). https://doi.org/10.1007/s00432-014-1780-6
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DOI: https://doi.org/10.1007/s00432-014-1780-6