Proteomic profiling and scRNA sequencing identify signatures associated with infection and risk of developing gastric cancer.

Objective: The key molecular events signifying the -induced gastric carcinogenesis process are largely unknown.

Methods: 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).

Results: 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).

Conclusions: Concordant proteomics signatures associated with infection and gastric carcinogenesis were unveiled with potential as biomarkers for targeted prevention strategies.