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

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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

Fingerprint

RNA-Binding Proteins
Somatomedins
Colorectal Neoplasms
Messenger RNA
Confidence Intervals
Microsatellite Instability
Mutation
CpG Islands
Molecular Epidemiology
Rectal Neoplasms
Tumor Biomarkers
Proportional Hazards Models
Colonic Neoplasms
Methylation
Mucous Membrane
Epithelium
Biomarkers
Immunohistochemistry
Databases
Carcinoma

Keywords

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

Cite this

Insulin-like growth factor 2 messenger RNA binding protein 3 (IGF2BP3) is a marker of unfavourable prognosis in colorectal cancer. / Lochhead, Paul; Imamura, Yu; Morikawa, Teppei; Kuchiba, Aya; Yamauchi, Mai; Liao, Xiaoyun; Qian, Zhi Rong; Nishihara, Reiko; Wu, Kana; Meyerhardt, Jeffrey A; Fuchs, Charles S; Ogino, Shuji.

In: European Journal of Cancer, Vol. 48, No. 18, 12.2012, p. 3405-3413.

Research output: Contribution to journalArticle

Lochhead, P, Imamura, Y, Morikawa, T, Kuchiba, A, Yamauchi, M, Liao, X, Qian, ZR, Nishihara, R, Wu, K, Meyerhardt, JA, Fuchs, CS & 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, vol. 48, no. 18, pp. 3405-3413. https://doi.org/10.1016/j.ejca.2012.06.021
Lochhead, Paul ; Imamura, Yu ; Morikawa, Teppei ; Kuchiba, Aya ; Yamauchi, Mai ; Liao, Xiaoyun ; Qian, Zhi Rong ; Nishihara, Reiko ; Wu, Kana ; Meyerhardt, Jeffrey A ; Fuchs, Charles S ; Ogino, Shuji. / Insulin-like growth factor 2 messenger RNA binding protein 3 (IGF2BP3) is a marker of unfavourable prognosis in colorectal cancer. In: European Journal of Cancer. 2012 ; Vol. 48, No. 18. pp. 3405-3413.
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title = "Insulin-like growth factor 2 messenger RNA binding protein 3 (IGF2BP3) is a marker of unfavourable prognosis in colorectal cancer",
abstract = "BackgroundEvidence 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 methodsWe 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.ResultsAmong 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).ConclusionsIGF2BP3 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.",
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T1 - Insulin-like growth factor 2 messenger RNA binding protein 3 (IGF2BP3) is a marker of unfavourable prognosis in colorectal cancer

AU - Lochhead, Paul

AU - Imamura, Yu

AU - Morikawa, Teppei

AU - Kuchiba, Aya

AU - Yamauchi, Mai

AU - Liao, Xiaoyun

AU - Qian, Zhi Rong

AU - Nishihara, Reiko

AU - Wu, Kana

AU - Meyerhardt, Jeffrey A

AU - Fuchs, Charles S

AU - Ogino, Shuji

N1 - PMID: 22840368 [PubMed - indexed for MEDLINE] PMCID: PMC3613860 Free PMC Article

PY - 2012/12

Y1 - 2012/12

N2 - BackgroundEvidence 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 methodsWe 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.ResultsAmong 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).ConclusionsIGF2BP3 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.

AB - BackgroundEvidence 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 methodsWe 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.ResultsAmong 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).ConclusionsIGF2BP3 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.

KW - adenocarcinoma

KW - rectal cancer

KW - cancer testis antigen

KW - MAGE

KW - carcinogenesis

KW - diagnostic marker

KW - pathology

KW - therapeutic target

KW - personalised medicine

U2 - 10.1016/j.ejca.2012.06.021

DO - 10.1016/j.ejca.2012.06.021

M3 - Article

C2 - 22840368

VL - 48

SP - 3405

EP - 3413

JO - European Journal of Cancer

JF - European Journal of Cancer

SN - 0959-8049

IS - 18

ER -