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DNA methylation and expression profiling study for bladder cancer [methylation]

ABSTRACT: The DNA methylation patterns associated with the development and progression of cancer. The aim of the present study was to identify novel methylation markers that can discriminate between normal and Non-muscle-invasive bladder cancer (NMIBC), and between good and poor prognosis using microarray analysis of DNA methylation and RNA expression patterns in NMIBC patients. From the 24 matched microarray-based DNA methylation and gene expression profiling data set, tumor specific hypermethylated genes were selected and clinical relevance of these genes were verified by quantitative PQS analyses. Methylation statues of several genes were significantly associated with decreased gene expression levels and aggressive clinicopathological characteristics. In multivariate regression analyses, hypermethylation of these genes were the independent predictors of recurrence and progression.

ORGANISM(S): Homo sapiens

PROVIDER: GSE37816 | GEO | 2013/05/03

SECONDARY ACCESSION(S): PRJNA163667

REPOSITORIES: GEO

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Project description:Lung cancer is the worldwide leading cause of death from cancer. DNA methylation in gene promoter regions is a major mechanism of gene expression regulation that may promote tumorigenesis. However, whether clinically relevant subgroups based on DNA methylation patterns exist in lung cancer is not well studied. We performed whole-genome methylation analysis using 450K Illumina BeadArrays on 124 tumors including 83 adenocarcinomas, 23 squamous cell carcinomas, one adenosquamous cancer, five large cell carcinomas, nine large cell neuroendocrine carcinomas (LCNEC), three small cell carcinomas (SCLC) and 12 normal lung tissues. Unsupervised class discovery was performed to identify DNA methylation subgroups with clinicopathological and molecular features. Subgroups were validated in two independent NSCLC cohorts. Unsupervised analysis identified five DNA methylation subgroups (epitypes). One epitype was distinctly associated with neuroendocrine tumors (LCNEC and SCLC). For adenocarcinoma, in both discovery and validation cohorts, remaining four epitypes were associated with differences in clinicopathological and molecular features, including global hypomethylation, promoter hypermethylation, copy number alterations, expression of proliferation-associated genes, association with unsupervised and supervised gene expression phenotypes, KRAS, TP53, KEAP1, SMARCA4, and STK11 mutations, smoking history, and patient outcome. Based on a multicohort approach we conducted a comprehensive survey of genome-wide DNA methylation in lung cancer, identifying a distinct neuroendocrine epitype and four adenocarcinoma epitypes associated with molecular and clinicopathological characteristics, and patient outcome. Our results bring further understanding of the epigenetic characteristics and molecular diversity in lung cancer generally and in adenocarcinoma specifically. Genome-wide DNA methylation analysis of 124 lung carcinomas and 12 normal lung tissues using Illumina Human Methylation 450K v1.0 Beadchips.

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DNA methylation and expression profiling study for bladder cancer [methylation]

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