Methylation-based Cell-free DNA Signature for Early Detection of Pancreatic Cancer. Issue 9 (3rd October 2021)

• Record Type: Journal Article
• Authors: Ying, Lee; Sharma, Anup; Chhoda, Ankit; Ruzgar, Nensi; Hasan, Nesrin; Kwak, Ruby; Wolfgang, Christopher L.; Wang, Tza Huei; Kunstman, John W.; Salem, Ronald R.; Wood, Laura D.; Iacobuzio-Donahue, Christine; Schneider, Eric B.; Farrell, James J.; Ahuja, Nita
• Is Part Of: Pancreas. Volume 50:Issue 9(2021)
• Page Start: 1267
• Page End: 1273
• Publication Date: 2021-10-03
• Subjects: cell-free DNA -- methylation -- pancreatic cancer -- CP - chronic pancreatitis -- PanIN - pancreatic intraepithelial neoplasia -- IPMN - intraductal papillary mucinous neoplasia -- ADAMTS1 - a disintegrin and metalloproteinase with thrombospondin motifs -- BNC1 - zinc finger protein basonuclin-1 -- LRFN5 - leucine-rich repeat and fibronectin type III domain containing 5 -- PXDN - peroxidasin -- cfDNA - cell-free DNA; Pancreas -- Diseases -- Periodicals; Pancreas -- Periodicals; Neuroendocrine tumors -- Periodicals; 616.37005
• DOI: 10.1097/MPA.0000000000001919
• Languages: English
• ISSNs: 0885-3177

Abstract

Abstract : Objectives: The potential of DNA methylation alterations in early pancreatic cancer (PC) detection among pancreatic tissue cell-free DNA seems promising. This study investigates the diagnostic capacity of the 4-gene methylation biomarker panel, which included ADAMTS1, BNC1, LRFN5, and PXDN genes, in a case-control study. Methods: A genome-wide pharmacoepigenetic approach identified ADAMTS1, BNC1, LRFN5, and PXDN genes as putative targets. Tissue samples including stage I–IV PC (n = 44), pancreatic intraepithelial neoplasia (n = 15), intraductal papillary mucinous neoplasms (n = 24), and normal pancreas (n = 8), and cell-free DNA, which was acquired through methylation on beads technology from PC (n = 22) and control patients (n = 10), were included. The 2 −∆ct was the outcome of interest and underwent receiver operating characteristic analysis to determine the diagnostic accuracy of the panel. Results: Receiver operating characteristic analysis revealed an area under the curve of 0.93 among ADAMTS1, 0.76 among BNC1, 0.75 among PXDN, and 0.69 among LRFN5 gene. The combination gene methylation panel ( ADAMTS1, BNC1, LRFN5, and PXDN ) had an area under the curve of 0.94, with a sensitivity of 100% and specificity of 90%. Conclusions: This methylation-based biomarker panel had promising accuracy for PC detection and warranted further validation in prospective PC surveillance trials.