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J Cancer Res Clin Oncol. 2015 Jan;141(1):35-41. doi: 10.1007/s00432-014-1780-6. Epub 2014 Jul 31.

Genetic variation in microRNA-binding site and prognosis of patients with colorectal cancer.

Author information

1
Department of Oncology/Hematology, Kyungpook National University Medical Center, Kyungpook National University School of Medicine, Daegu, Republic of Korea, jkk21c@mail.knu.ac.kr.

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.

PMID:
25079514
DOI:
10.1007/s00432-014-1780-6
[Indexed for MEDLINE]
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