title: Insulin-like growth factor 2 messenger RNA binding protein 3 (IGF2BP3) is a marker of unfavourable prognosis in colorectal cancer.
abstract: BACKGROUND
  Evidence suggests that insulin-like growth factor 2 messenger RNA binding protein 3 (IGF2BP3, also known as IMP3) represents a promising cancer biomarker. However, the clinical, pathological, molecular and prognostic features of IGF2BP3-positive colorectal cancers remain uncertain.
  
  
  METHODS
  We evaluated IGF2BP3 expression by immunohistochemistry in 671 rectal and colon cancer cases that form part of a molecular pathological epidemiology database. Cox proportional hazards regression models were used to compute mortality hazard ratio (HR), adjusting for clinical, pathological and molecular features, including microsatellite instability, the CpG island methylator phenotype, LINE-1 methylation and KRAS, BRAF and PIK3CA mutations.
  
  
  RESULTS
  Among 671 colorectal cancers, 234 (35%) tumours were positive for IGF2BP3. In contrast, normal colorectal epithelium was negative for IGF2BP3 in all 403 specimens of normal mucosa adjacent to carcinoma. IGF2BP3 positivity was associated with poor differentiation (p=0.0003), stage III-IV disease (p=0.0081), BRAF mutation (p=0.031), and LINE-1 hypomethylation (p=0.020). IGF2BP3 positivity was significantly associated with shorter colorectal cancer-specific [log-rank p<0.0001; multivariate HR, 1.37; 95% confidence interval (CI), 1.02-1.84] and overall survival (log-rank p=0.0004; multivariate HR, 1.32; 95% CI, 1.05-1.66).
  
  
  CONCLUSIONS
  IGF2BP3 expression in colorectal cancer is associated with adverse clinical outcome. Our findings support a role for IGF2BP3 as a diagnostic and/or prognostic biomarker in colorectal cancer.
authors: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, United States. paul.lochhead@channing.harvard.edu
authors: Paul
authors: P
authors: Lochhead
authors: Yu
authors: Y
authors: Imamura
authors: Teppei
authors: T
authors: Morikawa
authors: Aya
authors: A
authors: Kuchiba
authors: Mai
authors: M
authors: Yamauchi
authors: Xiaoyun
authors: X
authors: Liao
authors: Zhi Rong
authors: ZR
authors: Qian
authors: Reiko
authors: R
authors: Nishihara
authors: Kana
authors: K
authors: Wu
authors: Jeffrey A
authors: JA
authors: Meyerhardt
authors: Charles S
authors: CS
authors: Fuchs
authors: Shuji
authors: S
authors: Ogino
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000737:chemistry* / Q000235:genetics / Q000401:mortality; D014408:Biomarkers, Tumor / Q000032:analysis*; D018279:Carcinoma, Signet Ring Cell / Q000737:chemistry* / Q000235:genetics / Q000401:mortality; D002454:Cell Differentiation; D058534:Class I Phosphatidylinositol 3-Kinases; D015331:Cohort Studies; D003110:Colonic Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000401:mortality; D018899:CpG Islands; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D011905:Genes, ras; D006801:Humans; D020084:Long Interspersed Nucleotide Elements; D008297:Male; D053842:Microsatellite Instability; D009154:Mutation; D009363:Neoplasm Proteins / Q000032:analysis*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D011379:Prognosis; D016016:Proportional Hazards Models; D011518:Proto-Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D016601:RNA-Binding Proteins / Q000032:analysis*; D012004:Rectal Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000401:mortality; D014481:United States / Q000453:epidemiology; D018631:ras Proteins / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; C498780:IGF2BP3 protein, human; C117307:KRAS protein, human; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D016601:RNA-Binding Proteins; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins