diagnosis of bladder cancer recurrence based on urinary levels of eomes, hoxa9, pou4f2, twist1, vim, and znf154 hypermethylation基于尿膀胱癌复发的诊断水平的加工,hoxa9,pou4f2,twist1,vim,znf154甲基化.pdfVIP

Diagnosis of Bladder Cancer Recurrence Based on Urinary Levels of EOMES, HOXA9, POU4F2, TWIST1, VIM, and ZNF154 Hypermethylation 1 2 1 3 1 Thomas Reinert , Michael Borre , Anders Christiansen , Gregers G. Hermann , Torben F. Ørntoft , Lars Dyrskjøt1* 1 Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark, 2 Department of Urology, Aarhus University Hospital, Aarhus, Denmark, 3 Department of Urology, Frederiksberg Hospital, Copenhagen University, Frederiksberg, Denmark Abstract Background: Non muscle invasive bladder cancer (NMIBC) has the highest recurrence rate of any malignancy and as many as 70% of patients experience relapse. Aberrant DNA methylation is present in all bladder tumors and can be detected in urine specimens. Previous studies have identified DNA methylation markers that showed significant diagnostic value. We evaluated the significance of the biomarkers for early detection of tumor recurrence in urine. Methodology/Principal Findings: The methylation levels of EOMES, HOXA9, POU4F2, TWIST1, VIM, and ZNF154 in urine specimens were measured by real-time PCR (MethyLight). We analyzed 390 urine sediments from 184 patients diagnosed with NMIBC. Urine from 35 age-matched control individuals was used to determine the methylation baseline levels. Recurrence was diagnosed by cystoscopy and verified by histology. Initially, we compared urine from bladder cancer patients and healthy individuals and detected significant hypermethylation of all six markers (P,0.0001) achieving sensitivity in the range 82%–89% and specificity in the range 94%–100%. Following, we validated the urinary hypermethylation for