title: Cumulative methylation alternations of gene promoters and protein markers for diagnosis of epithelial ovarian cancer.
abstract: DNA methylation plays an important role in carcinogenesis and cancer development. In this study, we examined gene methylation in epithelial ovarian cancer (EOC) using cationic conjugated polymer (CCP)-based fluorescence resonance energy transfer (FRET) to evaluate the application of cumulative methylation alternations of genes associated with cancer antigen 125 for early cancer diagnosis. The methylation status of 3 genes (Ras association domain family 1 isoform A, RASSF1A; opioid-binding protein/cell adhesion molecule, OPCML; homeobox A9, HOXA9) were examined and compared in 35 EOC samples and 11 normal ovarian tissue samples using CCP-based FRET. Gene methylation levels were clustered into 3 sections and assigned a value; values for the 3 genes were summed. Although methylation of the OPCML gene was significantly associated with stage, histological types, grade, and ascites and that of RASSF1A and HOXA9 was not, the sum for the 3 genes was significantly associated with stage and ascites. The sum showed higher sensitivity (85.7%) and specificity (100%) for discriminating EOC from normal ovarian tissues than did the methylation status of RASSF1A, OPCML, and HOXA9 (48.6, 77.1, 77.1, and 100, 88.1, 100%, respectively). Combining cancer antigen 125 levels with the sum increased the sensitivity to 94.3%. The detection and analysis of a panel of genes' methylation status with the CCP-based FRET technique may be useful for diagnosis and screening of EOC; the associated cancer antigen 125 can be used to increase diagnostic sensitivity.
authors.affiliation: Department of Pathology, Changzhou Maternal and Child Health Care Hospital, Changzhou, China 793506861@qq.com.
authors.forename: B L
authors.initials: BL
authors.lastname: Xing
authors.affiliation: Department of Pathology, Changzhou Maternal and Child Health Care Hospital, Changzhou, China.
authors.forename: T
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Pathology, Changzhou Maternal and Child Health Care Hospital, Changzhou, China.
authors.forename: Z H
authors.initials: ZH
authors.lastname: Tang
authors.affiliation: Department of Pathology, Changzhou Maternal and Child Health Care Hospital, Changzhou, China.
authors.forename: L
authors.initials: L
authors.lastname: Jiao
authors.affiliation: Department of Pathology, Changzhou Maternal and Child Health Care Hospital, Changzhou, China.
authors.forename: S M
authors.initials: SM
authors.lastname: Ge
authors.affiliation: Department of Pathology, Changzhou Maternal and Child Health Care Hospital, Changzhou, China.
authors.forename: X
authors.initials: X
authors.lastname: Qiang
authors.affiliation: Department of Pathology, Changzhou Maternal and Child Health Care Hospital, Changzhou, China.
authors.forename: J
authors.initials: J
authors.lastname: OuYang
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D000077216:Carcinoma, Ovarian Epithelial; D015815:Cell Adhesion Molecules / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D031541:Fluorescence Resonance Energy Transfer; D058851:GPI-Linked Proteins / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000175:diagnosis / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000235:genetics*; D011401:Promoter Regions, Genetic; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; D058851:GPI-Linked Proteins; D018398:Homeodomain Proteins; C059785:OPCML protein, human; C411762:RASSF1 protein, human; D025521:Tumor Suppressor Proteins; C097899:homeobox protein HOXA9