Objective: The key molecular events signifying the Helicobacter pylori-induced gastric carcinogenesis process are largely unknown. Methods: Bulk tissue-proteomics profiling were leveraged across multi-stage gastric lesions from Linqu (n 166) and Beijing sets (n 99) and single-cell transcriptomic profiling (n 18) to decipher key molecular signatures of H. pylori-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 (n 48,529). Results: Concordant proteomics signatures associated with H. pylori infection and gastric carcinogenesis ( 0.784, correlation P 1.80 1036) 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: 1.3139.72 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: 1.638.54, high-risk vs. low-risk populations, area under the curve 0.75). Conclusions: Concordant proteomics signatures associated with H. pylori infection and gastric carcinogenesis were unveiled with potential as biomarkers for targeted prevention strategies.
Jin et al. (Thu,) studied this question.
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