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This study aimed to identify\n                    <jats:italic>H. pylori<\/jats:italic>\n                    -related genes in GC and elucidate their molecular functions. Transcriptomic data from TCGA and GEO databases were analyzed using weighted gene co-expression network analysis (WGCNA), LASSO regression, and multivariate Cox analysis to construct a prognostic model. The immune landscape was also assessed. Validation involved RT-qPCR and immunohistochemistry (IHC). An\n                    <jats:italic>in vitro H. pylori<\/jats:italic>\n                    co-culture system was used to assess time-dependent changes in gene and protein expression via RT-qPCR, IHC, and Western blotting. A four-gene risk model\n                    <jats:italic>(PDCD1<\/jats:italic>\n                    ,\n                    <jats:italic>KYNU<\/jats:italic>\n                    ,\n                    <jats:italic>CYTL1<\/jats:italic>\n                    ,\n                    <jats:italic>and FZD2)<\/jats:italic>\n                    was identified, demonstrating strong predictive capacity for overall survival as an independent prognostic factor. High-risk patients exhibited reduced immune cell infiltration. CellMiner analysis identified potential therapeutic agents targeting these genes. Among them,\n                    <jats:italic>KYNU<\/jats:italic>\n                    showed significant upregulation in GC tissues. Notably, in the co-culture system,\n                    <jats:italic>KYNU<\/jats:italic>\n                    expression markedly increased at both mRNA and protein levels following\n                    <jats:italic>H. pylori<\/jats:italic>\n                    infection in a time-dependent manner. The\n                    <jats:italic>H. pylori<\/jats:italic>\n                    -associated risk model represents a novel independent prognostic indicator for GC. Particularly,\n                    <jats:italic>KYNU<\/jats:italic>\n                    emerged as a pivotal gene in\n                    <jats:italic>H. pylori<\/jats:italic>\n                    -mediated GC, offering insights into disease progression and serving as a promising therapeutic target.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-59676-4","type":"journal-article","created":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T11:26:47Z","timestamp":1782559607000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comprehensive bioinformatics analysis identifies KYNU as a novel Helicobacter pylori -associated biomarker with prognostic and therapeutic potential in gastric cancer"],"prefix":"10.1038","volume":"16","author":[{"given":"Yangyang","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruofan","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiantong","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dandan","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongwei","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,27]]},"reference":[{"issue":"10251","key":"59676_CR1","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1016\/S0140-6736(20)31288-5","volume":"29","author":"EC Smyth","year":"2020","unstructured":"Smyth, E. 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Approval was granted by the Institute Research Ethics Committee at Shandong Provincial Hospital (Date: SWYX: NO.2022\u2009\u2212\u2009326). We explained the purpose and experimental procedures to the patients and got their signed informed consent in the study.","order":2,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"29576"}}