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.
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.
Authors: Hongjuan Zhao; Anita Langerød; Youngran Ji; Kent W Nowels; Jahn M Nesland; Rob Tibshirani; Ida K Bukholm; Rolf Kåresen; David Botstein; Anne-Lise Børresen-Dale; Stefanie S Jeffrey Journal: Mol Biol Cell Date: 2004-03-19 Impact factor: 4.138
Authors: Gokce A Toruner; Celal Ulger; Mualla Alkan; Anthony T Galante; Joseph Rinaggio; Randall Wilk; Bin Tian; Patricia Soteropoulos; Meera R Hameed; Marvin N Schwalb; James J Dermody Journal: Cancer Genet Cytogenet Date: 2004-10-01
Authors: Yee Soo Chae; Jong Gwang Kim; Byung Woog Kang; Soo Jung Lee; Yoo Jin Lee; Jun Seok Park; Gyu Seog Choi; Won Kee Lee; Hyo-Sung Jeon Journal: Anticancer Res Date: 2013-02 Impact factor: 2.480
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Authors: Juan Xu; Xiyun Deng; Min Tang; Lili Li; Lanbo Xiao; Lifang Yang; Juanfang Zhong; Ann M Bode; Zigang Dong; Yongguang Tao; Ya Cao Journal: PLoS One Date: 2013-03-05 Impact factor: 3.240