HOXA9, ISL1, and ALDH1A3 methylation patterns as prognostic markers for non-muscle invasive bladder cancer: Array-based DNA methylation and expression profiling.

Kim YJ, Yoon HY, Kim JS, Kang HW, Min BD, Kim SK, Ha YS, Kim IY, Ryu KH, Lee SC, Kim WJ.

Source

Department of Urology, College of Medicine, Chungbuk National University, Cheongju, South Korea.

Abstract

DNA methylation patterns are associated with the development and prognosis of cancer. The aim of the present study was to identify novel methylation markers for the prediction of patient outcomes using microarray analysis of DNA methylation and RNA expression patterns in samples from long-term follow-up patients with non-muscle invasive bladder cancer (NMIBC). A total of 187 human bladder specimens were used for microarray array or pyrosequencing (PSQ) analyses: 6 normal controls (NC) and 181 NMIBC. Tumor-specific hypermethylated genes were selected from a data set comprising 24 matched microarray-based DNA methylation and gene expression profiles (6 controls and 18 NMIBC), and their clinical relevance was verified by quantitative PSQ analysis. The methylation status of Homeobox A9 (HOXA9), ISL LIM homeobox 1 (ISL1), and Aldehyde dehydrogenase 1 family, member A3 (ALDH1A3) was significantly associated with decreased gene expression levels and aggressive clinicopathological characteristics. Multivariate regression analyses showed that hypermethylation of these genes was an independent predictor of disease recurrence (HOXA9, ISL1, and ALDH1A3, either alone or in combination) and progression (ISL1 and ALDH1A3, either alone or in combination) (each p < 0.05). The results of the present study suggest that these novel methylation markers are independent prognostic indicators in NMIBC patients, which may facilitate the assessment of disease recurrence and progression in NMIBC patients and inform clinical decision making regarding treatment. © 2013 Wiley Periodicals, Inc.
Copyright © 2013 UICC.