Dataset Information

Methylomic analysis identifies frequent DNA methylation of zinc finger protein 582 (ZNF582) in cervical neoplasms.

ABSTRACT: Despite of the trend that the application of DNA methylation as a biomarker for cancer detection is promising, clinically applicable genes are few. Therefore, we looked for novel hypermethylated genes for cervical cancer screening.At the discovery phase, we analyzed the methylation profiles of human cervical carcinomas and normal cervixes by methylated DNA immunoprecipitation coupled to promoter tiling arrays (MeDIP-on-chip). Methylation-specific PCR (MSP), quantitative MSP and bisulfite sequencing were used to verify the methylation status in cancer tissues and cervical scrapings from patients with different severities. Immunohistochemical staining of a cervical tissue microarray was used to confirm protein expression. We narrowed to three candidate genes: DBC1, PDE8B, and ZNF582; their methylation frequencies in tumors were 93%, 29%, and 100%, respectively. At the pre-validation phase, the methylation frequency of DBC1 and ZNF582 in cervical scraping correlated significantly with disease severity in an independent cohort (n?=?330, both P<0.001). For the detection of cervical intraepithelial neoplasia 3 (CIN3) and worse, the area under the receiver operating characteristic curve (AUC) of ZNF582 was 0.82 (95% confidence interval=?0.76-0.87).Our study shows ZNF582 is frequently methylated in CIN3 and worse lesions, and it is demonstrated as a potential biomarker for the molecular screening of cervical cancer.

SUBMITTER: Huang RL

PROVIDER: S-EPMC3397950 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Methylomic analysis identifies frequent DNA methylation of zinc finger protein 582 (ZNF582) in cervical neoplasms.

Huang Rui-Lan RL Chang Cheng-Chang CC Su Po-Hsuan PH Chen Yu-Chih YC Liao Yu-Ping YP Wang Hui-Chen HC Yo Yi-Te YT Chao Tai-Kuang TK Huang Hsuan-Cheng HC Lin Ching-Yu CY Chu Tang-Yuan TY Lai Hung-Cheng HC

PloS one 20120716 7

<h4>Background</h4>Despite of the trend that the application of DNA methylation as a biomarker for cancer detection is promising, clinically applicable genes are few. Therefore, we looked for novel hypermethylated genes for cervical cancer screening.<h4>Methods and findings</h4>At the discovery phase, we analyzed the methylation profiles of human cervical carcinomas and normal cervixes by methylated DNA immunoprecipitation coupled to promoter tiling arrays (MeDIP-on-chip). Methylation-specific P ...[more]

PMID: 22815913

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Project description:Background DNA methylation is implicated in many chronic diseases and may contribute to mortality. Therefore, we conducted an epigenome-wide association study (EWAS) for all-cause mortality with whole-transcriptome data in a cardiovascular cohort (CATHGEN [Catheterization Genetics]). Methods and Results Cases were participants with mortality≥7 days postcatheterization whereas controls were alive with≥2 years of follow-up. The Illumina Human Methylation 450K and EPIC arrays (Illumina, San Diego, CA) were used for the discovery and validation sets, respectively. A linear model approach with empirical Bayes estimators adjusted for confounders was used to assess difference in methylation (Δβ). In the discovery set (55 cases, 49 controls), 25 629 (6.5%) probes were differently methylated (P<0.05). In the validation set (108 cases, 108 controls), 3 probes were differentially methylated with a false discovery rate-adjusted P<0.10: cg08215811 (SLC4A9; log2 fold change=-0.14); cg17845532 (MATK; fold change=-0.26); and cg17944110 (castor zinc finger 1 [CASZ1]; FC=0.26; P<0.0001; false discovery rate-adjusted P=0.046-0.080). Meta-analysis identified 6 probes (false discovery rate-adjusted P<0.05): the 3 above, cg20428720 (intergenic), cg17647904 (NCOR2), and cg23198793 (CAPN3). Messenger RNA expression of 2 MATK isoforms was lower in cases (fold change=-0.24 [P=0.007] and fold change=-0.61 [P=0.009]). The CASZ1, NCOR2, and CAPN3 transcripts did not show differential expression (P>0.05); the SLC4A9 transcript did not pass quality control. The cg17944110 probe is located within a potential regulatory element; expression of predicted targets (using GeneHancer) of the regulatory element, UBIAD1 (P=0.01) and CLSTN1 (P=0.03), were lower in cases. Conclusions We identified 6 novel methylation sites associated with all-cause mortality. Methylation in CASZ1 may serve as a regulatory element associated with mortality in cardiovascular patients. Larger studies are necessary to confirm these observations.

Dataset Information

Methylomic analysis identifies frequent DNA methylation of zinc finger protein 582 (ZNF582) in cervical neoplasms.

Publications

Methylomic analysis identifies frequent DNA methylation of zinc finger protein 582 (ZNF582) in cervical neoplasms.

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