{
  "abstract": "Background To investigate metabolic alterations of gastric cancer (GC) with or without Helicobacter pylori (H. pylori) infection and depict key pathway dynamics at single-cell resolution across disease stages.Methods 165 Plasma samples from GC cases and controls (superficial gastritis, SG) with various H. pylori infection statuses were collected from a high-risk area for GC in China based on the National Upper Gastrointestinal Cancer Early Detection Program. H.pylori status was defined using 13C-urea breath tests in conjunction with serum antibody assays. Broad-targeted metabolomic analysis was conducted and differential metabolites were identified by variable importance in projection, false discovery rate and fold change. Kyoto Encyclopedia of Genes and Genomes annotation and enrichment analysis were subsequently performed. A public single-cell RNA sequencing dataset comprising 18 specimens of SG, intestinal metaplasia (IM) and GC was utilized to validate the expression trends of pathway-related genes and pathway activity in different cell types. The workflow overview was shown in Figure 1 (IDDF2026-ABS-0360 Figure 1. The study design and workflow overview).Results As Figure 2 ( IDDF2026-ABS-0360 Figure 2. H.pylori status-specific metabolic signatures and reprogramming patterns in gastric carcinogenesis) demonstrated, 1991 metabolites were detected and 16 differential metabolites were identified (14 upregulated, 2 downregulated) between H. pylori-positive and -negative GC. To explore the perturbations of biological pathways, we included 377 metabolites which led to the enrichment of 7 key pathways. A total of 442 pathway-related human genes were retrieved. Choline metabolism was the only significantly upregulated pathway in malignant cells, while others showed downregulation. Choline metabolism peaked in gland mucous cells and POSTN+ cancer-associated fibroblasts, revealing metabolic reprogramming extended to the tumor microenvironment. Retrograde endocannabinoid signaling was most active in parietal, proliferative, and endocrine cells and its downregulation in malignant cells implied tumor-suppressive functions lost during carcinogenesis. H. pylori-positive cases may display an‘early-onset’pattern with metabolic activation already at the IM stage, while H. pylori-negative GC exhibited a‘late-onset’pattern with activation occurring at the GC stage.Conclusions H. pylori status influences the metabolic signatures and reprogramming patterns in gastric carcinogenesis. H. pylori-positive patients may benefit from early intervention at the IM stage to reverse metabolic alterations, while H. pylori-negative patients have a longer window for surveillance. These findings provide novel insights into metabolism-based molecular mechanisms of gastric pathogenesis and a precision prevention strategy for GC.Abstract IDDF2026-ABS-0360 Figure 1Abstract IDDF2026-ABS-0360 Figure 2",
  "authors": [
    {
      "affiliations": [
        "State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China"
      ],
      "name": "Yu-Xin Wang"
    },
    {
      "affiliations": [
        "State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China"
      ],
      "name": "Yu Jin"
    },
    {
      "affiliations": [
        "State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China"
      ],
      "name": "Zong-Chao Liu"
    },
    {
      "affiliations": [
        "Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital and Institute, Haidian District, Beijing, China"
      ],
      "name": "Yang Zhang"
    },
    {
      "affiliations": [
        "State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China"
      ],
      "name": "Wen-Qing Li"
    },
    {
      "affiliations": [
        "State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China"
      ],
      "name": "Kai-Feng Pan"
    }
  ],
  "title": "IDDF2026-ABS-0360 Identification of H.pylori status-specific metabolic signatures and reprogramming patterns in gastric carcinogenesis",
  "uid": "cf885b35-8459-5fb7-9458-fc6f60d706b3"
}