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2014-08-15

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cc-by (c) Perez-Carbonell, Lucia et al., 2014
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/122281

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

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https://doi.org/10.1371/journal.pone.0104285

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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.

Matèries

Càncer colorectal, Marcadors bioquímics, Metilació, ADN, Estudi de casos, Diagnòstic

Matèries (anglès)

Colorectal cancer, Biochemical markers, Methylation, DNA, Case studies, Diagnosis

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Articles publicats en revistes (Medicina)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

Citació

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. IGFBP3 methylation is a novel diagnostic and predictive biomarker in colorectal cancer. _PLoS One_. 2014. Vol. 9, núm. 8, pàgs. e104285. [consulta: 25 de desembre de 2025]. ISSN: 1932-6203. [Disponible a: https://hdl.handle.net/2445/122281]

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