Methylation profile of circulating plasma DNA in patients with pancreatic cancer

J Surg Oncol. 2009 Feb 1;99(2):119-22. doi: 10.1002/jso.21208.

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 Five-fold 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / blood*
  • Carcinoma, Pancreatic Ductal / blood
  • Carcinoma, Pancreatic Ductal / diagnosis
  • Carcinoma, Pancreatic Ductal / genetics*
  • DNA / blood
  • DNA Methylation*
  • Female
  • Genetic Markers
  • Humans
  • Male
  • Microarray Analysis
  • Middle Aged
  • Pancreatic Neoplasms / blood
  • Pancreatic Neoplasms / diagnosis
  • Pancreatic Neoplasms / genetics*
  • Sensitivity and Specificity

Substances

  • Biomarkers, Tumor
  • Genetic Markers
  • DNA