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- Title
Methylomic Analysis Identifies Frequent DNA Methylation of Zinc Finger Protein 582 (ZNF582) in Cervical Neoplasms.
- Authors
Rui-Lan Huang; Cheng-Chang Chang; Po-Hsuan Su; Yu-Chih Chen; Yu-Ping Liao; Hui-Chen Wang; Yi-Te Yo; Tai-Kuang Chao; Hsuan-Cheng Huang; Ching-Yu Lin; Tang-Yuan Chu; Hung-Cheng Lai
- Abstract
Background: 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. Methods and Findings: 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). Methylationspecific 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). Conclusions: 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.
- Subjects
DNA methylation; ZINC-finger proteins; TUMORS; IMMUNOPRECIPITATION; CANCER patients; CANCER diagnosis
- Publication
PLoS ONE, 2012, Vol 7, Issue 7, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0041060