{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T05:59:50Z","timestamp":1790315990855,"version":"4.1.0"},"reference-count":92,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Gastric cancer (GC) is a heterogeneous malignancy that requires improved molecular tools for prognostic stratification. Protein palmitoylation regulates membrane localization and signaling, but the clinical relevance of palmitoylation-related genes (PRGs) in GC remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Gene Expression Omnibus, The Cancer Genome Atlas, and GeneCards data were integrated to identify PRGs. Differential expression analysis, weighted gene co-expression network analysis, and three machine-learning algorithms were used to select key genes. Diagnostic and prognostic performance was evaluated in TCGA-STAD, platform-specific GEO cohorts, and an institutional cohort of 80 paired tissues. Immune infiltration, single-cell RNA sequencing, immunotherapy-related indices, and GDSC-based drug sensitivity were analyzed. CTHRC1 was further examined using clinical specimens, cell assays, and xenografts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Thirteen differentially expressed PRGs were identified, and SERPINE1, CTHRC1, and EGR1 were selected. The integrated diagnostic model achieved AUCs of 0.935 in TCGA-STAD, 1.000 in GSE54129, and 0.916 in GSE118916, respectively. The three-gene score stratified overall survival in the total, training, and testing TCGA-STAD cohorts and in GSE84437, GSE236522, and the institutional cohort. It remained independently associated with survival in multivariable analysis. High-risk tumors showed increased stromal and immune scores, altered immune-cell composition, higher checkpoint expression, and higher TIDE scores. Single-cell analysis localized SERPINE1 and CTHRC1 mainly to fibroblast-related compartments. CTHRC1 knockdown reduced GC-cell proliferation, clonogenicity, migration, invasion, and xenograft growth while increasing apoptosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The SERPINE1\/CTHRC1\/EGR1 signature provides prognostic and immune-stromal information in GC, and the experiments support a tumor-promoting role for CTHRC1. The findings define a palmitoylation-associated transcriptional framework but do not establish a palmitoylation-dependent mechanism.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1893438","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T05:32:02Z","timestamp":1790314322000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["A palmitoylation-associated three-gene signature predicts prognosis, immune features, and drug sensitivity in gastric cancer: functional validation of CTHRC1"],"prefix":"10.3389","volume":"17","author":[{"given":"Hongmei","family":"Sheng","sequence":"first","affiliation":[{"name":"Second Department of Geriatrics, The Second Affiliated Hospital of Anhui University of Chinese Medicine","place":["Hefei, 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