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.
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.
Authors: Elisa Cassinotti; Joshua Melson; Thomas Liggett; Anatoliy Melnikov; Qilong Yi; Charles Replogle; Sohrab Mobarhan; Luigi Boni; Sergio Segato; Victor Levenson Journal: Int J Cancer Date: 2011-11-19 Impact factor: 7.396
Authors: Caitlin M Stewart; Prachi D Kothari; Florent Mouliere; Richard Mair; Saira Somnay; Ryma Benayed; Ahmet Zehir; Britta Weigelt; Sarah-Jane Dawson; Maria E Arcila; Michael F Berger; Dana Wy Tsui Journal: J Pathol Date: 2018-03-12 Impact factor: 7.996