{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T14:46:13Z","timestamp":1784126773199,"version":"3.55.0"},"reference-count":63,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,5,10]],"date-time":"2022-05-10T00:00:00Z","timestamp":1652140800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p><jats:italic>Helicobacter pylori<\/jats:italic> (HP), a gram-negative spiral-shaped microaerophilic bacterium, colonizes the stomach of approximately 50% of the world\u2019s population, which is considered a risk factor for gastritis, peptic ulcers, gastric cancer, and other malignancies. HP is also considered carcinogenic since it involves the mutation and damage of multiple HP-related genes. Stomach adenocarcinoma (STAD) is a common stom5ach cancer with a poor prognosis and high risk of metastasis in the advanced stage. Therefore, an early diagnosis and targeted therapies are needed to ensure a better prognosis. In this study, a scoring system was constructed based on three HP infection\u2013related candidate genes to enable a more accurate prediction of tumor progression and metastasis and response to immunotherapies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>HP infection\u2013induced mutation patterns of STAD samples from six cohorts were comprehensively assessed based on 73 HP-related genes, which were then correlated with the immune cell\u2013infiltrating characteristics of the tumor microenvironment (TME). The risk signature was constructed to quantify the influence of HP infection on individual tumors. Subsequently, an accurate nomogram was generated to improve the clinical applicability of the risk signature. We conducted immunohistochemical experiments and used the Affiliated Hospital of Youjiang Medical University for Nationalities (AHYMUN) cohort data set with survival information to further verify the clinical value of this risk signature.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Two distinct HP-related mutation patterns with different immune cell\u2013infiltrating characteristics (ICIC) and survival possibility were identified. We demonstrated that the evaluation of HP infection\u2013induced mutation patterns of tumor could assist the prediction of stages, phenotypes, stromal activity, genetic diversity, and patient prognosis. A low risk score involved an increased mutation burden and activation of immune responses, with a higher 5-year survival rate and enhanced response to anti-PD-1\/L1 immunotherapy, while a high risk score involved stromal activation and poorer survival. The efficiency of the risk signature was further evidenced by the nomogram.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>STAD patients with a low risk score demonstrated significant therapeutic advantages and clinical benefits. HP infection\u2013induced mutations play a nonnegligible role in STAD development. Quantifying the HP-related mutation patterns of individual tumors will contribute to phenotype classification, guide more effective targeted and personalized therapies, and enable more accurate predictions of metastasis and prognosis.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcimb.2022.880636","type":"journal-article","created":{"date-parts":[[2022,5,10]],"date-time":"2022-05-10T07:21:51Z","timestamp":1652167311000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["A Multi-Omics Study on the Effect of Helicobacter Pylori-Related Genes in the Tumor Immunity on Stomach Adenocarcinoma"],"prefix":"10.3389","volume":"12","author":[{"given":"Xinrui","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiwen","family":"Jian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haidan","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wangrui","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengyuan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shifan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiqun","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,5,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"977","DOI":"10.1016\/S0140-6736(14)62038-9","article-title":"Global Surveillance of Cancer Survival 1995-2009: Analysis of Individual Data for 25,676,887 Patients From 279 Population-Based Registries in 67 Countries (CONCORD-2)","volume":"385","author":"Allemani","year":"2015","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1055","DOI":"10.3390\/cells9041055","article-title":"Mechanisms of the Epithelial-Mesenchymal Transition and Tumor Microenvironment in Helicobacter Pylori-Induced Gastric Cancer","volume":"9","author":"Baj","year":"2020","journal-title":"Cells"},{"key":"B3","doi-asserted-by":"publisher","first-page":"4334","DOI":"10.1128\/IAI.00553-07","article-title":"Expression of the Programmed Death Ligand 1, B7-H1, on Gastric Epithelial Cells After Helicobacter Pylori Exposure Promotes Development of CD4+ CD25+ FoxP3+ Regulatory T Cells","volume":"75","author":"Beswick","year":"2007","journal-title":"Infect. 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