Methylation profile of circulating plasma DNA in patients with pancreatic cancer

Anatoliy A. Melnikov, Denise Scholtens, Mark S. Talamonti, David J. Bentrem, Victor V. Levenson

Research output: Contribution to journalArticlepeer-review

73 Scopus citations

Abstract

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 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 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 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.

Original languageEnglish (US)
Pages (from-to)119-122
Number of pages4
JournalJournal of surgical oncology
Volume99
Issue number2
DOIs
StatePublished - Feb 1 2009

Keywords

  • Composite biomarker
  • DNA methylation
  • Detection
  • Pancreatic cancer

ASJC Scopus subject areas

  • Oncology
  • Surgery

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