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. 2021 Oct 1;50(9):1267-1273.
doi: 10.1097/MPA.0000000000001919.

Methylation-based Cell-free DNA Signature for Early Detection of Pancreatic Cancer

Lee Ying  1 , Anup Sharma  1 , Ankit Chhoda  2 , Nensi Ruzgar  1 , Nesrin Hasan  1 , Ruby Kwak  3 , Christopher L Wolfgang  4 , Tza Huei Wang  5 , John W Kunstman  1 , Ronald R Salem  1 , Laura D Wood  6 , Christine Iacobuzio-Donahue  7 , Eric B Schneider  1 , James J Farrell  2 , Nita Ahuja
Affiliations

Methylation-based Cell-free DNA Signature for Early Detection of Pancreatic Cancer

Lee Ying et al. Pancreas. .

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.

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Conflict of interest statement

N.A. receives research grant funding from Astex Inc and the Van Andel Research Institute. She is a consultant for and has licensed methylation biomarkers to Cepheid (patent # 10167513). N.A. has also served as a consultant to Johnson and Johnson, an advisor to Celgene, and a member of the Scientific Advisory Council to the No Stomach for Cancer Foundation. N.A. also serves as PI on NIH grants 5P30CA016359-42 and 7R01CA185357-05. This work was supported by the NIH grant 7R01CA185357-05. All authors have read the journal's policy on disclosure of potential conflicts of interest, and none of the authors have financial or personal relationship with organizations that could potentially be perceived as influencing the described research.

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