Methylation of the insulin-like growth factor binding protein-3 gene and prognosis of epithelial ovarian cancer.
Insulin-like growth factor binding protein-3 (IGFBP-3) is a member of the IGFBP family, which regulates the mitogenic and antiapoptotic effects of insulin-like growth factors. Hypermethylation of the IGFBP-3 promoter has been found to suppress its expression. To evaluate the role of IGFBP-3 in ovarian cancer progression, we examined the survival of 235 consecutively selected epithelial ovarian cancer patients in association with IGFBP-3 promoter methylation and IGFBP-3 expression in tumor tissue. IGFBP-3 promoter methylation was analyzed using methylation-specific polymerase chain reaction. Cytosol protein was extracted and measured using a bicinchoninic acid assay; IGFBP-3 was measured by enzyme linked immunosorbent assay. Promoter methylation of the IGFBP-3 gene was detected in 44% (104/235) of patients. IGFBP-3 promoter methylation was associated with disease progression and death after adjusting for clinical and pathologic variables. The association was more evident in patients with early-stage disease: RR = 2.87 (95% CI: 0.78-10.63) for disease progression and RR = 3.94 (95% CI: 0.91-15.78) for death. Tissue levels of IGFBP-3 did not differ by methylation status but were inversely associated with disease stage and residual tumor size. These results suggest that IGFBP-3 promoter methylation may be a useful prognostic marker for disease progression and death in early-stage ovarian cancer.
Wiley
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A
Department of Epidemiology and Public Health, Yale Cancer Center, Yale University School of Medicine, New Haven, CT 06520-8034, USA.
Katsaros
D
D
Fracchioli
S
S
Yu
H
H
D014408:Biomarkers, Tumor / Q000032:analysis*; D001707:Biopsy, Needle; D002277:Carcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D015331:Cohort Studies; D019175:DNA Methylation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics / Q000378:metabolism*; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D010052:Ovariectomy / Q000379:methods; D011336:Probability; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D012680:Sensitivity and Specificity; D015996:Survival Rate
D014408:Biomarkers, Tumor; D018972:Insulin-Like Growth Factor Binding Protein 3