{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T03:13:34Z","timestamp":1788578014728,"version":"build-2803163510"},"reference-count":46,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:00:00Z","timestamp":1788480000000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"publisher","award":["2023J011618"],"award-info":[{"award-number":["2023J011618"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["iubmb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BioFactors"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Macrophage heterogeneity is increasingly recognized as an important feature of the gastric cancer tumor microenvironment, yet the macrophage states linked to poor outcome and the molecules connecting them to stromal remodeling remain incompletely defined. Here, we integrated single\u2010cell RNA sequencing data from GSE183904, spatial transcriptomic data from GSE251950, and TCGA\u2010STAD bulk transcriptomic data to characterize macrophage diversity and identify clinically relevant macrophage\u2010associated genes. Cell\u2013cell communication analysis revealed intensified intercellular signaling in tumors, with prominent changes in MIF, COLLAGEN, FN1, LAMININ, and SPP1 pathways. Five macrophage subclusters were resolved. Among them, macro_SPP1 and macro_IL1B signatures were associated with shorter overall survival, whereas macro_C3_CX3CR1 was linked to a more favorable outcome. By integrating macro_SPP1 markers with tumor\u2010associated differentially expressed genes and applying Cox regression together with multiple machine learning approaches, SERPINE1 emerged as the most consistent prognostic candidate. High SERPINE1 expression was associated with poor survival and with stromal, myeloid, and vascular features. Spatial analysis further localized SERPINE1\u2010high regions to microenvironments enriched for fibroblast\u2010 and endothelial\u2010related components and for TGF\u2010\u03b2, hypoxia, inflammatory, and extracellular matrix remodeling programs. Virtual perturbation suggested that SERPINE1 may influence myeloid and matrix\u2010related transcriptional networks. Functionally, SERPINE1 knockdown reduced proliferation, colony formation, migration, and invasion in gastric cancer cells. Together, these findings identify SERPINE1 as a macro_SPP1\u2010associated molecule with prognostic and functional relevance and suggest a potential link between macrophage\u2010associated programs, stromal remodeling, and malignant behavior in gastric cancer.<\/jats:p>","DOI":"10.1002\/biof.70145","type":"journal-article","created":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T03:02:01Z","timestamp":1788577321000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated Single\u2010Cell and Spatial Transcriptomics Reveal\n                    <scp>SERPINE1<\/scp>\n                    as a Key Link Between Macro_SPP1 Macrophages and Stromal Remodeling in Gastric Cancer"],"prefix":"10.1002","volume":"52","author":[{"given":"Huangdao","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Gastrointestinal Oncology Surgery, The First Affiliated Hospital of Xiamen University, School of Medicine Xiamen University  Xiamen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhai","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Endoscopy Center, The First Affiliated Hospital of Xiamen University, School of Medicine Xiamen University  Xiamen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingqi","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Oncology Surgery, The First Affiliated Hospital of Xiamen University, School of Medicine Xiamen University  Xiamen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2328-8110","authenticated-orcid":false,"given":"Hexin","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Oncology Surgery, The First Affiliated Hospital of Xiamen University, School of Medicine Xiamen University  Xiamen 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