Urine proteomic signatures predicting the progression from premalignancy to malignant gastric cancer

作者：Hua Fan, Xue Li, Zhongwu Li, Nairen Zheng, Lihua Cao, Zongchao Liu, Mingwei Liu, Kai Li, Wenhui Wu, Zhexuan Li, Tong Zhou, Yang Zhang, Weidong Liu, Lan‐Fu Zhang, Wei‐Cheng You, Yi Wang, Jianmin Wu, Kai‐Feng Pan, Jun Qin, Wenqing Li · 发表于：EBioMedicine · 年份：2022 · DOI：10.1016/j.ebiom.2022.104340 · 被引用次数：31 · 研究领域：Ferroptosis and cancer prognosis、Gastric Cancer Management and Outcomes、Advanced Proteomics Techniques and Applications

BACKGROUND: 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. METHODS: 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. FINDINGS: 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). INTERPRETATION: This study revealed distinct urine proteomic profiles and a panel of proteins that may predict the progression of gastric lesions and risk of...