Differential methylation profile of ovarian cancer in tissues and plasma.
An accurate biomarker for detection of ovarian cancer may reduce cancer-related mortality. Using a previously developed microarray-based technique, we evaluated differences in DNA methylation profiles in a panel of 56 genes using sections of serous papillary adenocarcinomas and uninvolved ovaries (n=30) from women in a high-risk group. Methylation profiles were also generated for circulating DNA from blood of patients (n=33) and healthy controls (n=33). Using the most differentially methylated genes for naïve Bayesian analysis, we identified ten of these profiles as potentially informative in tissues. Various combinations of these genes produced 69% sensitivity and 70% specificity for cancer detection as estimated under a stratified, fivefold cross-validation protocol. In plasma, five genes were identified as informative; their combination had 85% sensitivity and 61% specificity for cancer detection. These results suggest that differential methylation profiling in heterogeneous samples has the potential to identify components of a composite biomarker that may detect ovarian cancer in blood with significant accuracy.
Melnikov
Anatoliy
A
Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
Scholtens
Denise
D
Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois; Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
Godwin
Andrew
A
Fox Chase Cancer Center, Department of Medical Oncology, Philadelphia, Pennsylvania.
Levenson
Victor
V
Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois. Electronic address: Victor_Levenson@rush.edu.
D000231:Adenocarcinoma, Papillary / Q000097:blood* / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D004247:DNA / Q000097:blood; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000097:blood; D005260:Female; D006801:Humans; D008875:Middle Aged; D009928:Organ Specificity; D010051:Ovarian Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D012680:Sensitivity and Specificity
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D004247:DNA