4.5 Article

Methylation Profile of Circulating Plasma DNA in Patients With Pancreatic Cancer

Journal

JOURNAL OF SURGICAL ONCOLOGY
Volume 99, Issue 2, Pages 119-122

Publisher

WILEY
DOI: 10.1002/jso.21208

Keywords

DNA methylation; composite biomarker; pancreatic cancer; detection

Funding

  1. Illinois Department of Public Health, Penny Severns Breast, Cervical, and Ovarian Cancer Research Fund

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Background and Objectives: 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 a-c-matched controls (it = 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 Fivefold cross-validation results indicate 76% sensitivity and 59% specificity of the biomarker, which included promoters of CCND2. SOCS1. THBS1, PLAU, and VHL. Conclusion: Differential methylation profiling of plasma DNA call 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.

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