BACKGROUND: Currently, no reliable blood-based assay for early detection of pancreatic ductal adenocarcinoma (PDAC) is available. Cell-free DNA (cfDNA) quantitation in patients' plasma has been recently applied in monitoring several cancer types. This study evaluates the diagnostic potential of cfDNA in PDAC patients. METHODS: Plasma cfDNA levels and integrity ratio were assayed using quantitative real-time PCR of Alu-repeat amplicons in patients with pancreatic ductal adenocarcinoma (n=50), pancreatic neuroendocrine tumor (n=23), and chronic pancreatitis (n=20), as well as in healthy volunteers without evidence of pancreatic disease (n=23). RESULTS: The total load of cfDNA, obtained by Alu83 quantitation, was the highest in PDAC patients than in any of the other patient groups (Welch t test; p<0.001) and was an average predictor of PDAC disease (AUC=0.664; CI, 0.56-0.77). A nonlinear association between Alu83 levels and subjects' age was detected (Spearman's rho=0.35; p<0.001) in the overall population, as well as within the PDAC patients' group (Spearman's rho=0.47; p<0.001). Necrosis-derived cfDNA fragments, quantitated with the Alu244 amplicon, were barely detectable in any of the samples and, in that respect, comparable between the different subject groups. CfDNA integrity estimation (Alu244/Alu83 ratio) was significantly affected by the limited detectability of plasma Alu244 levels. CONCLUSION: The lack of detectable levels of necrosis-derived cfDNA in pancreatic pathologies considerably affects the clinical use of such biomarker in PDAC patients. Different methods of analysis should be applied in the evaluation of the cfDNA diagnostic value in pancreas pathology.
BACKGROUND: Currently, no reliable blood-based assay for early detection of pancreatic ductal adenocarcinoma (PDAC) is available. Cell-free DNA (cfDNA) quantitation in patients' plasma has been recently applied in monitoring several cancer types. This study evaluates the diagnostic potential of cfDNA in PDAC patients. METHODS: Plasma cfDNA levels and integrity ratio were assayed using quantitative real-time PCR of Alu-repeat amplicons in patients with pancreatic ductal adenocarcinoma (n=50), pancreatic neuroendocrine tumor (n=23), and chronic pancreatitis (n=20), as well as in healthy volunteers without evidence of pancreatic disease (n=23). RESULTS: The total load of cfDNA, obtained by Alu83 quantitation, was the highest in PDAC patients than in any of the other patient groups (Welch t test; p&lt;0.001) and was an average predictor of PDAC disease (AUC=0.664; CI, 0.56-0.77). A nonlinear association between Alu83 levels and subjects' age was detected (Spearman's rho=0.35; p&lt;0.001) in the overall population, as well as within the PDAC patients' group (Spearman's rho=0.47; p&lt;0.001). Necrosis-derived cfDNA fragments, quantitated with the Alu244 amplicon, were barely detectable in any of the samples and, in that respect, comparable between the different subject groups. CfDNA integrity estimation (Alu244/Alu83 ratio) was significantly affected by the limited detectability of plasma Alu244 levels. CONCLUSION: The lack of detectable levels of necrosis-derived cfDNA in pancreatic pathologies considerably affects the clinical use of such biomarker in PDAC patients. Different methods of analysis should be applied in the evaluation of the cfDNA diagnostic value in pancreas pathology.
Authors: Thomas S Frank; Xiaotian Sun; Yuqing Zhang; Jingxuan Yang; William E Fisher; Marie-Claude Gingras; Min Li Journal: Cancer Lett Date: 2015-04-15 Impact factor: 8.679
Authors: Wesley K Utomo; Vincent T Janmaat; Auke P Verhaar; Jérôme Cros; Philippe Lévy; Philippe Ruszniewski; Mirella S Vredenbregt-van den Berg; Guido Jenster; Marco J Bruno; Henri Braat; Gwenny M Fuhler; Maikel P Peppelenbosch Journal: Am J Cancer Res Date: 2016-08-01 Impact factor: 6.166
Authors: Ian A Cree; Lesley Uttley; Helen Buckley Woods; Hugh Kikuchi; Anne Reiman; Susan Harnan; Becky L Whiteman; Sian Taylor Philips; Michael Messenger; Angela Cox; Dawn Teare; Orla Sheils; Jacqui Shaw Journal: BMC Cancer Date: 2017-10-23 Impact factor: 4.430
Authors: Claudio Luchini; Nicola Veronese; Alessia Nottegar; Vera Cappelletti; Maria G Daidone; Lee Smith; Christopher Parris; Lodewijk A A Brosens; Maria G Caruso; Liang Cheng; Christopher L Wolfgang; Laura D Wood; Michele Milella; Roberto Salvia; Aldo Scarpa Journal: Cancers (Basel) Date: 2019-08-10 Impact factor: 6.639