A Multi-Omics Study on the Effect of Helicobacter Pylori-Related Genes in the Tumor Immunity on Stomach Adenocarcinoma.

Background: Methods: HP infection-induced 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-infiltrating 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. Results: Two distinct HP-related mutation patterns with different immune cell-infiltrating characteristics (ICIC) and survival possibility were identified. We demonstrated that the evaluation of HP infection-induced 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. Conclusions: STAD patients with a low risk score demonstrated significant therapeutic advantages and clinical benefits. HP infection-induced 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.