Identification of biomarkers and potential therapeutic targets for pancreatic cancer by proteomic analysis in two prospective cohorts

Jingjing Lyu; Minghui Jiang; Ziwei Zhu; Hongji Wu; Haonan Kang; Xingjie Hao; Shanshan Cheng; Huan Guo; Xia Shen; Tangchun Wu; Jiang Chang; Chaolong Wang

doi:10.1016/j.xgen.2024.100561

Identification of biomarkers and potential therapeutic targets for pancreatic cancer by proteomic analysis in two prospective cohorts

Cell Genom. 2024 May 10:100561. doi: 10.1016/j.xgen.2024.100561. Online ahead of print.

Authors

Jingjing Lyu¹, Minghui Jiang¹, Ziwei Zhu¹, Hongji Wu¹, Haonan Kang¹, Xingjie Hao¹, Shanshan Cheng¹, Huan Guo², Xia Shen³, Tangchun Wu⁴, Jiang Chang⁵, Chaolong Wang⁶

Affiliations

¹ Ministry of Education Key Laboratory of Environment and Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
² Ministry of Education Key Laboratory of Environment and Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
³ Greater Bay Area Institute of Precision Medicine (Guangzhou), Fudan University, Guangzhou, China.
⁴ Ministry of Education Key Laboratory of Environment and Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: wut@tjmu.edu.cn.
⁵ Ministry of Education Key Laboratory of Environment and Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Department of Health Toxicology, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: changjiang815@hust.edu.cn.
⁶ Ministry of Education Key Laboratory of Environment and Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: chaolong@hust.edu.cn.

PMID: 38754433
DOI: 10.1016/j.xgen.2024.100561

Abstract

Pancreatic cancer (PC) is the deadliest malignancy due to late diagnosis. Aberrant alterations in the blood proteome might serve as biomarkers to facilitate early detection of PC. We designed a nested case-control study of incident PC based on a prospective cohort of 38,295 elderly Chinese participants with ∼5.7 years' follow-up. Forty matched case-control pairs passed the quality controls for the proximity extension assay of 1,463 serum proteins. With a lenient threshold of p < 0.005, we discovered regenerating family member 1A (REG1A), REG1B, tumor necrosis factor (TNF), and phospholipase A2 group IB (PLA2G1B) in association with incident PC, among which the two REG1 proteins were replicated using the UK Biobank Pharma Proteomics Project, with effect sizes increasing steadily as diagnosis time approaches the baseline. Mendelian randomization analysis further supported the potential causal effects of REG1 proteins on PC. Taken together, circulating REG1A and REG1B are promising biomarkers and potential therapeutic targets for the early detection and prevention of PC.

Keywords: Mendelian randomization; biomarker; circulating protein; incident pancreatic cancer; prospective study; risk stratification.