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

Zhu, Jingjing; Wu, Ke; Liu, Shuai; Masca, Alexandra; Zhong, Hua; Yang, Tai; Ghoneim, Dalia H.; Surendran, Praveen; Liu, Tanxin; Yao, Qizhi; Liu, Tao; Fahle, Sarah; Butterworth, Adam; Alam, Md Ashad; Vadgama, Jaydutt V.; Deng, Youping; Deng, Hong-Wen; Wu, Chong; Wu, Yong; Wu, Lang

doi:10.1093/gigascience/giae012

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

Journal Article · 11 April 2024 · GigaScience

DOI: https://doi.org/10.1093/gigascience/giae012 · OSTI ID:2471586

Zhu, Jingjing ^[1]; Wu, Ke ^[2]; Liu, Shuai ^[1]; Masca, Alexandra ^[1]; Zhong, Hua ^[1]; Yang, Tai ^[3]; Ghoneim, Dalia H. ^[1]; Surendran, Praveen ^[4]; Liu, Tanxin ^[5]; Yao, Qizhi ^[6]; Liu, Tao ^[7]; Fahle, Sarah ^[4]; Butterworth, Adam ^[4]; Alam, Md Ashad ^[8]; Vadgama, Jaydutt V. ^[2];

^[1];

^[8]; Wu, Chong ^[9]; Wu, Yong ^[2];

^[1]

University of Hawaii at Manoa, Honolulu, HI (United States)
Charles R. Drew University of Medicine and Science, Los Angeles, CA (United States); University of California, Los Angeles, CA (United States). David Geffen School of Medicine, Jonsson Comprehensive Cancer Center
University of Michigan, Ann Arbor, MI (United States)
University of Cambridge (United Kingdom)
Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (United States)
Baylor College of Medicine, Houston, TX (United States); Michael E. DeBakey VA Medical Center, Houston, TX (United States). Center for Translational Research on Inflammatory Diseases (CTRID)
Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)
Tulane University, New Orleans, LA (United States)
University of Texas MD Anderson Cancer Center, Houston, TX (Untied States)

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 2 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.

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Research Organization:: Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)

Sponsoring Organization:: Accelerating Excellence in Translational Science (AXIS); British Heart Foundation (BHF); Department of Defense Breast Cancer Research Program (DOD BCRP); Hawaii Advanced Training in Artificial Intelligence for Precision Nutrition Science Research (AIPrN); Medical Research Council (MRC); National Institutes of Health (NIH); USDOE; VA Office of Research and Development (VA-ORD)

Grant/Contract Number:: AC05-76RL01830

OSTI ID:: 2471586

Journal Information:: GigaScience, Journal Name: GigaScience Vol. 13; ISSN 2047-217X

Publisher:: BioMed CentralCopyright Statement

Country of Publication:: United States

Language:: English

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60 APPLIED LIFE SCIENCES
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biomarkers
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protein
risk

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

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