title: Genetic variation in microRNA-binding site and prognosis of patients with colorectal cancer.
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.
  
  
  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).
  
  
  CONCLUSIONS
  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: Department of Oncology/Hematology, Kyungpook National University Medical Center, Kyungpook National University School of Medicine, Daegu, Republic of Korea, jkk21c@mail.knu.ac.kr.
authors: Jong Gwang
authors: JG
authors: Kim
authors: Yee Soo
authors: YS
authors: Chae
authors: Soo Jung
authors: SJ
authors: Lee
authors: Byung Woog
authors: BW
authors: Kang
authors: Jae Yong
authors: JY
authors: Park
authors: Eun-Jin
authors: EJ
authors: Lee
authors: Hyo-Sung
authors: HS
authors: Jeon
authors: Jun Seok
authors: JS
authors: Park
authors: Gyu Seog
authors: GS
authors: Choi
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics*; D000230:Adenocarcinoma / Q000235:genetics / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001665:Binding Sites; D014408:Biomarkers, Tumor / Q000235:genetics; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D003131:Combined Modality Therapy; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D037102:Lectins / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D015238:Sulfotransferases / Q000235:genetics*; D015996:Survival Rate; D054928:Validation Studies as Topic; D055815:Young Adult
chemical_list: D020413:3' Untranslated Regions; D014408:Biomarkers, Tumor; D036341:Intercellular Signaling Peptides and Proteins; D037102:Lectins; D035683:MicroRNAs; C517340:ZG16B protein, human; D015238:Sulfotransferases; C039079:protein-tyrosine sulfotransferase