Abstract 1421: Non-invasive early detection of pancreatic ductal adenocarcinoma using methylation signatures in circulating tumor DNA

Abstract Background: Pancreatic ductal adenocarcinoma (PDAC) has a low overall survival rate primarily due to late onset of symptoms and rapid progression. Early symptoms, which include abdominal and back pain, diarrhea, weight loss, and jaundice are non-specific for PDAC and may be associated with other gastrointestinal diseases. PDAC lacks reliable and accurate tests for early detection. We aimed to discover biomarkers carrying a PDAC-specific DNA methylation signature in blood cell-free DNA, and to develop and validate a non-invasive test for PDAC detection. Methods: Reduced representative bisulfite sequencing (RRBS) was previously performed on tissue and plasma samples from PDAC patients and healthy individuals to identify PDAC-specific methylation markers. These markers were combined with previously reported cancer methylation markers for a second round of marker screening. The resulting markers were utilized to develop a targeted methylation sequencing assay for plasma DNA, designated as PDACatch. The PDACatch assay was validated on an independent sample set to demonstrate its efficacy for pancreatic cancer methylation signature detection. Results: The PDACatch assay was performed on 91 PDAC plasma and 84 healthy plasma samples obtained from commercial biobanks. In this independent verification sample set, the PandaX assay predicted PDAC from healthy with AUC of 0.91; accuracy remained high for classification of both stage I and early-stage (I/IIa) samples. Conclusion: The PDACatch assay, a ctDNA methylation based blood test, achieved a high accuracy for detecting PDAC at early stages, indicating its potential in screening effectiveness. Citation Format: Athurva J. Gore, Justin Dang, Alan Fung, Bin Xie, Rui Liu. Non-invasive early detection of pancreatic ductal adenocarcinoma using methylation signatures in circulating tumor DNA [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1421.