Differential methylation of cell-free circulating DNA among patients with pancreatic cancer versus chronic pancreatitis.
BACKGROUND
: Although patients with chronic pancreatitis (CP) have an increased risk of pancreatic cancer (PanCa), the timely detection of PanCa often is difficult, because the symptoms of CP and PanCa are very similar. Moreover, secondary inflammation may be identified in PanCa, further complicating diagnosis. To improve the survival of patients with PanCa, a reliable test to differentiate CP from PanCa is needed. In this article, the authors describe a methylation profile of cell-free plasma DNA that distinguished CP from PanCa with >90% accuracy.


METHODS
: Methylation in cell-free, plasma DNA was compared among 30 samples from patients with CP, 30 samples from patients with PanCa, and 30 samples from healthy controls (N) using a microarray-mediated methylation analysis of 56 fragments in each sample (MethDet56). Statistical analysis was done by using the Fisher exact test, a naive Bayes algorithm, and 25 rounds of 5-fold cross-validation.


RESULTS
: The MethDet56 methylation analysis technique identified 17 gene promoters as informative (8 for distinguishing N from CP and 14 for distinguishing CP from PanCa). It achieved 81.7% sensitivity and 78% specificity (P<.01) in the detection of CP (N vs CP) and 91.2% sensitivity and 90.8% specificity (P<.01) in the differential detection of PanCa (PanCa vs CP).


CONCLUSIONS
: The current data suggested that, among patients with pancreatic disease, the methylation profiles of inflammatory disease and cancer are different and open a new venue for the development of biomarkers for differential diagnosis. Further investigation of diagnostic biomarkers for pancreatic cancer based on methylation in cell-free, circulating DNA appears to be warranted. Cancer 2010. (c) 2010 American Cancer Society.
Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois.
Thomas
T
Liggett
Anatoliy
A
Melnikov
Qi-Long
QL
Yi
Charles
C
Replogle
Randall
R
Brand
Karen
K
Kaul
Mark
M
Talamonti
Ross A
RA
Abrams
Victor
V
Levenson
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood; D004247:DNA / Q000097:blood; D019175:DNA Methylation; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000097:blood / Q000235:genetics*; D050500:Pancreatitis, Chronic / Q000097:blood / Q000235:genetics*; D054928:Validation Studies as Topic
D014408:Biomarkers, Tumor; D004247:DNA