Abstract 2344: Novel multiplex paired-antibody amplified detection (MPAD) assay panel in combination with CA19-9 for early detection of pancreatic cancer using plasma samples

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with one of the lowest five-year survival rates among major cancers, due to asymptomatic progression and the lack of reliable biomarkers for early detection. CA19-9, the only FDA-approved biomarker related to PDAC, is significantly elevated in many individuals with PDAC, but falls short as a single marker early-detection screen due to its high levels of false negatives and positives. Therefore, identifying a novel biomarker panel to orthogonally buttress CA19-9’s sensitivity and specificity is critical for enhancing early PDAC detection. Objectives: This study is aimed to identify and test protein biomarkers and develop a non-invasive, high performing, affordable diagnostic screen for early-stage PDAC. Methods: The study cohort included matched healthy controls, patients with benign pancreatic conditions, and early- and late-stage PDAC patients. A Multiplex Paired-Antibody Amplified Detection (MPAD) platform uses paired antibodies conjugated with unique DNA barcodes and optimized epitope selection. Specific read-out is done using NGS. This approach enables the simultaneous detection of multiple biomarkers in a single well. Signal amplification techniques enhance the sensitivity and accuracy of detecting low-abundance biomarkers frequently associated with PDAC. Results: Using rigorous selection criteria, we designed a novel MPAD panel containing multiple protein targets as biomarkers for PDAC detection. These biomarkers demonstrated significant effect size for differentiating PDAC from non-cancer samples, and demonstrating low correlation with CA19-9, underscoring their complementary nature for this diagnostic application. The combination panel increased sensitivity from 58% (CA19-9 alone) to 89% for All PDAC vs. non-cancer samples, at a specificity of 96% and an AUC of 95.8%. While, for early-stage PDAC vs. non-cancer samples, the sensitivity was increased from 50% (CA19-9 alone) to 90% in the MPAD panel + CA19-9, suggesting that the MPAD panel can effectively buttress CA19-9 and that the combination shows potential as the basis for an early-detection diagnostic. In PDAC samples with low levels of CA19-9, the MPAD panel without CA19-9 showed strong discrimination between PDAC vs. both benign pancreatic and healthy control samples, with sensitivity of 80% and AUC of 86%, suggesting that the MPAD panel has potential to effectively salvage false negative samples missed by CA19-9 alone. Conclusions: The MPAD panel complements CA19-9 with minimal correlation, providing an independent diagnostic advantage. It significantly enhances the sensitivity of early-stage PDAC detection, particularly in patients with low CA19-9, making it a promising basis for early diagnosis and surveillance. Disclosure: AI was used for abstract text editing. Citation Format: Malcolm MacKenzie, Matthew Preimesberger, Shu Feng Zhou, Ilya Alexandrov. Novel multiplex paired-antibody amplified detection (MPAD) assay panel in combination with CA19-9 for early detection of pancreatic cancer using plasma samples [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2344.