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Title: IGFBP3 methylation is a novel diagnostic and predictive biomarker in colorectal cancer
Author: Perez-Carbonell, Lucia
Balaguer Prunés, Francesc
Toiyama, Yuji
Egoavil, Cecilia
Rojas, Estefania
Guarinos, Carla
Andreu, Montserrat
Llor, Xavier
Castells Garangou, Antoni
Jover, Rodrigo
Boland, C.Richard
Goel, Ajay
Keywords: Càncer colorectal
Marcadors bioquímics
Estudi de casos
Colorectal cancer
Biochemical markers
Case studies
Issue Date: 15-Aug-2014
Publisher: Public Library of Science (PLoS)
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.
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It is part of: PLoS One, 2014, vol. 9, num. 8, p. e104285
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ISSN: 1932-6203
Appears in Collections:Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Medicina)

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