Methylomic analysis identifies frequent DNA methylation of zinc finger protein 582 (ZNF582) in cervical neoplasms.
PLoS One, 2012;7(7):e41060.
Huang RL[1], Chang CC, Su PH, Chen YC, Liao YP, Wang HC, Yo YT, Chao TK, Huang HC, Lin CY, Chu TY, Lai HC
Affiliations
PMID: 22815913DOI: 10.1371/journal.pone.0041060
Impact factor: 3.752
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). 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).
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.
MeSH terms
3',5'-Cyclic-AMP Phosphodiesterases; Biomarkers; Cell Cycle Proteins; CpG Islands; DNA Methylation; Female; Gene Expression Regulation, Neoplastic; HeLa Cells; Humans; Kruppel-Like Transcription Factors; Nerve Tissue Proteins; Polymerase Chain Reaction; Promoter Regions, Genetic; ROC Curve; Tumor Suppressor Proteins; Uterine Cervical Neoplasms; Zinc Fingers
More resources
Full text:
Europe PubMed Central; PubMed Central
EndNote: Download