Abstract 6153: Proteome-wide association study and functional validation identify novel protein markers for pancreatic ductal adenocarcinoma

Abstract Pancreatic ductal adenocarcinoma (PDAC) remains a lethal malignancy, largely due to the paucity of reliable biomarkers for early detection and therapeutic targeting. Existing blood protein biomarkers for PDAC often suffer from replicability issues, arising from inherent limitations such as unmeasured confounding factors in conventional epidemiologic study designs. To circumvent these limitations, we use genetic instruments to identify proteins with genetically predicted levels to be associated with PDAC risk. Leveraging genome and plasma proteome data from the INTERVAL study, we established and validated models to predict protein levels using genetic variants. By examining 8,275 PDAC cases and 6,723 controls, we identified 40 associated proteins, of which 16 are novel. Functionally validating these candidates by focusing on two selected novel protein-encoding genes, GOLM1 and B4GALT1, we demonstrated their pivotal roles in driving PDAC cell proliferation, migration, and invasion. Furthermore, we also identified potential drug repurposing opportunities for treating PDAC. Our dual approach enhances our understanding of PDAC etiology and potentially opens new avenues for therapeutic interventions. Citation Format: Jingjing Zhu, Ke Wu, Shuai Liu, Alexandra Masca, Hua Zhong, Tai Yang, Dalia H. Ghoneim, Praveen Surendran, Tanxin Liu, Qizhi Yao, Tao Liu, Sarah Fahle, Adam Butterworth, Md A. Alam, Jaydutt V. Vadgama, Youping Deng, Hong-Wen Deng, Chong Wu, Yong Wu, Lang Wu. Proteome-wide association study and functional validation identify novel protein markers for pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6153.