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

IF 11.1 Q1 CELL BIOLOGY Cell genomics Pub Date : 2024-06-12 Epub Date: 2024-05-15 DOI:10.1016/j.xgen.2024.100561
Jingjing Lyu, Minghui Jiang, Ziwei Zhu, Hongji Wu, Haonan Kang, Xingjie Hao, Shanshan Cheng, Huan Guo, Xia Shen, Tangchun Wu, Jiang Chang, Chaolong Wang
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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.

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通过对两个前瞻性队列进行蛋白质组分析,确定胰腺癌的生物标志物和潜在治疗靶点。
胰腺癌(PC)因诊断较晚而成为最致命的恶性肿瘤。血液蛋白质组的异常改变可作为生物标志物,有助于早期发现胰腺癌。我们设计了一项巢式病例对照研究,研究对象是38 295名随访时间在5.7年以上的中国老年人。40对匹配的病例对照通过了1463种血清蛋白的近似延伸检测质量控制。以 p
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