Jin Yu, Li Xue, Cai Bingyao, Yang Lanxin, Zhao Wenjing, Xu Hengmin, Zhang Yang, Liu Zongchao, Pan Kaifeng, Li Wenqing
State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Peking University Cancer Hospital & Institute, Beijing 100142, China.
Department of Cancer Prevention, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou 310022, China.
Cancer Biol Med. 2025 Sep 4;22(8). doi: 10.20892/j.issn.2095-3941.2025.0077.
The key molecular events signifying the -induced gastric carcinogenesis process are largely unknown.
Bulk tissue-proteomics profiling were leveraged across multi-stage gastric lesions from Linqu ( = 166) and Beijing sets ( = 99) and single-cell transcriptomic profiling ( = 18) to decipher key molecular signatures of -related gastric lesion progression and gastric cancer (GC) development. The association of key proteins association with gastric lesion progression and GC development were prospectively studied building on follow-up of the Linqu set and UK Biobank ( = 48,529).
Concordant proteomics signatures associated with infection and gastric carcinogenesis (ρ = 0.784, correlation = 1.80 × 10) were identified. RNA expression of genes encoding 13 up- and 15 down-regulated key proteins displayed trending alterations in the transition from normal gastric epithelium to intestinal metaplasia, then to malignant cells. A 15-tissue protein panel integrating these signatures demonstrated potential for targeting individuals at high risk for progressing to gastric neoplasia (OR = 7.22, 95% CI: 1.31-39.72 for the high-score group). A 4-circulating protein panel may be used as non-invasive markers predicting the risk of GC development (hazard ratio = 3.73, 95% confidence interval: 1.63-8.54, high-risk low-risk populations, area under the curve = 0.75).
Concordant proteomics signatures associated with infection and gastric carcinogenesis were unveiled with potential as biomarkers for targeted prevention strategies.
标志幽门螺杆菌诱导胃癌发生过程的关键分子事件在很大程度上尚不清楚。
利用来自临朐（n = 166）和北京队列（n = 99）的多阶段胃病变的组织蛋白质组学分析以及单细胞转录组分析（n = 18），来破译幽门螺杆菌相关胃病变进展和胃癌（GC）发生的关键分子特征。基于临朐队列和英国生物银行（n = 48,529）的随访，前瞻性研究关键蛋白与胃病变进展和GC发生的关联。
鉴定出与幽门螺杆菌感染和胃癌发生相关的一致蛋白质组学特征（ρ = 0.784，相关性P = 1.80×10⁻¹⁰）。编码13种上调和15种下调关键蛋白的基因的RNA表达在从正常胃上皮向肠化生，再到恶性细胞的转变过程中呈现出趋势性变化。整合这些特征的15种组织蛋白组显示出针对进展为胃肿瘤高风险个体的潜力（高分组合的OR = 7.22，95%CI：1.31 - 39.72）。一个由4种循环蛋白组成的蛋白组可作为预测GC发生风险的非侵入性标志物（风险比 = 3.73，95%置信区间：1.63 - 8.54，高风险与低风险人群，曲线下面积 = 0.75）。
揭示了与幽门螺杆菌感染和胃癌发生相关的一致蛋白质组学特征，具有作为靶向预防策略生物标志物的潜力。
