Insulin-like growth factor 2 messenger RNA binding protein 3 (IGF2BP3) is a marker of unfavourable prognosis in colorectal cancer

Paul Lochhead, Yu Imamura, Teppei Morikawa, Aya Kuchiba, Mai Yamauchi, Xiaoyun Liao, Zhi Rong Qian, Reiko Nishihara, Kana Wu, Jeffrey A Meyerhardt, Charles S Fuchs, Shuji Ogino

Research output: Contribution to journalArticle

48 Citations (Scopus)

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.

Materials and 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.
Original languageEnglish
Pages (from-to)3405-3413
Number of pages9
JournalEuropean Journal of Cancer
Volume48
Issue number18
DOIs
Publication statusPublished - Dec 2012

Keywords

  • adenocarcinoma
  • rectal cancer
  • cancer testis antigen
  • MAGE
  • carcinogenesis
  • diagnostic marker
  • pathology
  • therapeutic target
  • personalised medicine

Fingerprint Dive into the research topics of 'Insulin-like growth factor 2 messenger RNA binding protein 3 (IGF2BP3) is a marker of unfavourable prognosis in colorectal cancer'. Together they form a unique fingerprint.

  • Cite this

    Lochhead, P., Imamura, Y., Morikawa, T., Kuchiba, A., Yamauchi, M., Liao, X., Qian, Z. R., Nishihara, R., Wu, K., Meyerhardt, J. A., Fuchs, C. S., & Ogino, S. (2012). Insulin-like growth factor 2 messenger RNA binding protein 3 (IGF2BP3) is a marker of unfavourable prognosis in colorectal cancer. European Journal of Cancer, 48(18), 3405-3413. https://doi.org/10.1016/j.ejca.2012.06.021