{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T10:50:19Z","timestamp":1792752619707,"version":"4.5.0"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,5]],"date-time":"2025-05-05T00:00:00Z","timestamp":1746403200000},"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. Immunol."],"abstract":"\n Background<\/jats:title>\n \n TNFRSF12A<\/jats:italic>\n is abnormally expressed in various malignancies, especially in stomach adenocarcinoma (STAD), which is related to tumor invasiveness and prognosis of patients. This study examined the expression pattern of\n TNFRSF12A<\/jats:italic>\n in STAD and predicted immunotherapy response.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Data were derived from The Cancer Gene Atlas (TCGA), Gene Expression Omnibus (GEO), and Gene Expression Profiling Interactive Analysis (GEPIA) to analyze the expression pattern of\n TNFRSF12A<\/jats:italic>\n in pan-cancer and STAD, as well as its correlation with clinical features. Biological pathways involved in\n TNFRSF12A<\/jats:italic>\n were analyzed by \u201cclusterProfiler\u201d package. Immune cell infiltration was evaluated by \u201cGSVA\u201d and \u201cCIBERSORT\u201d packages. Immunotherapy response was assessed by TIDE score and tumor mutation burden (TMB) level. Expression level of\n TNFRSF12A<\/jats:italic>\n in the single cell of STAD was analyzed by scRNA-seq. Finally,\n in vitro<\/jats:italic>\n test detected the mRNA expression of\n TNFRSF12A<\/jats:italic>\n in STAD cells, Wound healing and Transwell assays were performed to measure the capabilities of STAD cell to migrate and invade.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n TNFRSF12A<\/jats:italic>\n was highly expressed in STAD. However,\n TNFRSF12A<\/jats:italic>\n expression did not shown significant difference in relation to clinical features.\n TNFRSF12A<\/jats:italic>\n exhibited notably positive correlation with many carcinogenic signaling pathways and immune cells infiltration such as T cells and macrophages. High\n TNFRSF12A<\/jats:italic>\n expression group showed a higher TIDE score, Exclusion score, and TMB level than the low\n TNFRSF12A<\/jats:italic>\n expression group, which indicated that STAD patients with high\n TNFRSF12A<\/jats:italic>\n expression responded more poorly to immunotherapy.\n TNFRSF12A<\/jats:italic>\n showed a positive relation with most of immune checkpoint genes. By scRNA-seq analysis,\n TNFRSF12A<\/jats:italic>\n was chiefly expressed in Fibroblasts and Mast cells of STAD. Further,\n in vitro<\/jats:italic>\n assays verified the high expression of\n TNFRSF12A<\/jats:italic>\n in STAD cells, and the migration and invasion capabilities of STAD cells were notably suppressed by\n TNFRSF12A<\/jats:italic>\n silencing (\n p<\/jats:italic>\n &lt;0.05).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n The present study not only reveals the potential of\n TNFRSF12A<\/jats:italic>\n as a therapeutic target for STAD, but also explores its great potential in STAD immunotherapy. This finding opens up a new way of thinking for the personalized treatment of STAD.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1578068","type":"journal-article","created":{"date-parts":[[2025,5,5]],"date-time":"2025-05-05T01:10:35Z","timestamp":1746407435000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["TNFRSF12A expression in stomach adenocarcinoma and its preliminary role in predicting immunotherapy 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