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PLoS One. 2014 Aug 15;9(8):e104285. doi: 10.1371/journal.pone.0104285. eCollection 2014.

IGFBP3 methylation is a novel diagnostic and predictive biomarker in colorectal cancer.

Author information

1
Division of Gastroenterology, Department of Internal Medicine, Charles Sammons Cancer Center and Baylor Research Institute, Baylor University Medical Center, Dallas, Texas, United States of America.
2
Gastroenterology Department, Hospital Clinic, CIBERehd, IDIBAPS, University of Barcelona, Barcelona, Spain.
3
Department of Pathology, Hospital General Universitario de Alicante, Alicante, Spain.
4
Research Unit, Hospital General Universitario de Alicante, Alicante, Spain.
5
Gastroenterology Department, Hospital del Mar, Barcelona, Spain.
6
Department of Medicine and Cancer Center, University of Illinois at Chicago, Chicago, Illinois, United States of America.
7
Unidad de Gastroenterología, Hospital General Universitario de Alicante, Alicante, Spain.

Abstract

BACKGROUND AND AIM:

Aberrant hypermethylation of cancer-related genes has emerged as a promising strategy for the development of diagnostic, prognostic and predictive biomarkers in human cancer, including colorectal cancer (CRC). The aim of this study was to perform a systematic and comprehensive analysis of a panel of CRC-specific genes as potential diagnostic, prognostic and predictive biomarkers in a large, population-based CRC cohort.

PATIENTS AND METHODS:

Methylation status of the SEPT9, TWIST1, IGFBP3, GAS7, ALX4 and miR137 genes was studied by quantitative bisulfite pyrosequencing in a population-based cohort of 425 CRC patients.

RESULTS:

Methylation levels of all genes analyzed were significantly higher in tumor tissues compared to normal mucosa (p<0.0001); however, cancer-associated hypermethylation was most frequently observed for miR137 (86.7%) and IGFBP3 (83%) in CRC patients. Methylation analysis using the combination of these two genes demonstrated greatest accuracy for the identification of colonic tumors (sensitivity 95.5%; specificity 90.5%). Low levels of IGFBP3 promoter methylation emerged as an independent risk factor for predicting poor disease free survival in stage II and III CRC patients (HR = 0.49, 95% CI: 0.28-0.85, p = 0.01). Our results also suggest that stage II & III CRC patients with high levels of IGFBP3 methylation do not benefit from adjuvant 5FU-based chemotherapy.

CONCLUSION:

By analyzing a large, population-based CRC cohort, we demonstrate the potential clinical significance of miR137 and IGFBP3 hypermethylation as promising diagnostic biomarkers in CRC. Our data also revealed that IGFBP3 hypermethylation may serve as an independent prognostic and predictive biomarker in stage II and III CRC patients.

PMID:
25127039
PMCID:
PMC4134211
DOI:
10.1371/journal.pone.0104285
[Indexed for MEDLINE]
Free PMC Article
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