Methylation profile of circulating plasma DNA in patients with pancreatic cancer.
OBJECTIVE
Detection of pancreatic cancer by blood-based test may improve outcomes. We sought to establish the feasibility of a blood-based detection of pancreatic cancer through multiplexed array-mediated analysis of DNA methylation.


METHODS
Methylation was assessed in each plasma sample using a panel of 56 frequently methylated genes. Methylation profiles in patients with ductal cell adenocarcinoma of the pancreas (n = 30) and healthy gender and age-matched controls (n = 30) were compared. Methylation was determined as described previously; a composite biomarker was developed for classification of cancer and normal samples. Sensitivity and specificity of the biomarker were estimated using 25 rounds of fivefold cross-validation.


RESULTS
Five promoters were consistently selected for the classifier during cross-validation and comprised the final composite biomarker Five-fold cross-validation results indicate 76% sensitivity and 59% specificity of the biomarker, which included promoters of CCND2, SOCS1, THBS1, PLAU, and VHL.


CONCLUSIONS
Differential methylation profiling of plasma DNA can detect ductal adenocarcinoma of the pancreas with significant accuracy and should be explored further. While additional improvement of biomarkers is necessary, the blood-based biomarker may be already useful as a first-line detection tool.
Melnikov
Anatoliy A
AA
Robert H Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Scholtens
Denise
D
Talamonti
Mark S
MS
Bentrem
David J
DJ
Levenson
Victor V
VV
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D021441:Carcinoma, Pancreatic Ductal / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D004247:DNA / Q000097:blood; D019175:DNA Methylation; D005260:Female; D005819:Genetic Markers; D006801:Humans; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D012680:Sensitivity and Specificity
D014408:Biomarkers, Tumor; D005819:Genetic Markers; D004247:DNA