Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing 100142, China.
Department of Pathology, Peking University Cancer Hospital & Institute, Beijing 100142, China.
EBioMedicine. 2022 Dec;86:104340. doi: 10.1016/j.ebiom.2022.104340. Epub 2022 Nov 7.
Early detection of gastric cancer (GC) remains challenging. We aimed to examine urine proteomic signatures and identify protein biomarkers that predict the progression of gastric lesions and risk of GC.
A case-control study was initially designed, covering subjects with GC and gastric lesions of different stages. Subjects were aged 40-69 years, without prior diagnosis of renal or urological diseases. We enrolled a total of 255 subjects, with 123 in the discovery stage from Linqu, China, a high-risk area for GC and 132 in the validation stage from Linqu and Beijing. A prospective study was further designed for a subset of 60 subjects with gastric lesions, which were followed for 297-857 days.
We identified 43 differentially expressed urine proteins in subjects with GC vs. mild or advanced gastric lesions. Baseline urinary levels of ANXA11, CDC42, NAPA and SLC25A4 were further positively associated with risk of gastric lesion progression. Three of them, except for SLC25A4, also had higher expression in GC than non-GC tissues. Integrating these four proteins showed outstanding performance in predicting the progression of gastric lesions (AUC (95% CI): 0.92 (0.83-1.00)) and risk of GC (AUC (95% CI): 0.81 (0.73-0.89) and 0.84 (0.77-0.92) for GC vs. mild or advanced gastric lesions respectively).
This study revealed distinct urine proteomic profiles and a panel of proteins that may predict the progression of gastric lesions and risk of GC. These biomarkers in a non-invasive approach may have translational significance for defining high-risk populations of GC and its early detection.
Funders are listed in the Acknowledgement.
早期胃癌（GC）的检测仍然具有挑战性。我们旨在检查尿液蛋白质组学特征，并确定预测胃病变进展和 GC 风险的蛋白质生物标志物。
最初设计了一项病例对照研究，涵盖了 GC 和不同阶段胃病变的患者。患者年龄在 40-69 岁之间，没有肾脏或泌尿系统疾病的既往诊断。我们共招募了 255 名受试者，其中 123 名来自中国高风险地区临朐的发现阶段，132 名来自临朐和北京的验证阶段。进一步对 60 名胃病变患者进行了前瞻性研究，这些患者随访了 297-857 天。
我们在 GC 患者与轻度或晚期胃病变患者中鉴定出 43 种差异表达的尿液蛋白。基线尿液中 ANXA11、CDC42、NAPA 和 SLC25A4 的水平与胃病变进展的风险呈正相关。除了 SLC25A4 之外，这三个蛋白在 GC 组织中的表达也高于非 GC 组织。整合这四个蛋白在预测胃病变进展（AUC（95%CI）：0.92（0.83-1.00））和 GC 风险（AUC（95%CI）：0.81（0.73-0.89）和 0.84（0.77-0.92））方面表现出色。
本研究揭示了不同的尿液蛋白质组学特征和一组可能预测胃病变进展和 GC 风险的蛋白质。这些非侵入性方法中的生物标志物可能对确定 GC 的高危人群及其早期检测具有转化意义。
资助者在致谢中列出。
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