Epigenetic Inactivation of SFRP Genes and TP53 Alteration Act Jointly as Markers of Invasive Bladder Cancer

摘要: In the United States each year, almost 13,000 deaths are attributable to bladder cancer, with majority of these related higher stage, muscle-invasive solid tumors. Epigenetic silencing secreted frizzled receptor proteins (SFRP), antagonists WNT pathway, leads constitutive signaling, altering cell morphology and motility. Identifying alterations in this pathway cancer may prove useful for defining invasive phenotype provide targets guiding therapy. Using a population-based study (n = 355), we examined epigenetic alterations, specifically gene promoter hypermethylation, four SFRP genes addition immunohistochemical staining TP53, which has been previously shown be predictor disease. We observed significant linear trend (P 30-fold risk disease patients both altered methylation intense TP53 (odds ratio, 32.1; P < 10(-13)). Overall patient survival was significantly poorer any methylated 0.0003) proportional hazards modeling, had overall (hazard 1.78; 0.02) controlled intensity other survival-associated factors. Classifying tumors based on status protein clinically powerful invasive, deadly