{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:46:20Z","timestamp":1787013980828,"version":"build-2736575974"},"reference-count":52,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T00:00:00Z","timestamp":1763683200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T00:00:00Z","timestamp":1763683200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    To clarify locations and mutually exclusive subsets of SPP1\n                    <jats:sup>+<\/jats:sup>\n                    tumor associated macrophages (SPP1\n                    <jats:sup>+<\/jats:sup>\n                    TAMs) in lung adenocarcinoma (LUAD). Analyze the polarization type, mutually exclusive cell subset, and spatial location of SPP1\n                    <jats:sup>+<\/jats:sup>\n                    TAMs based on the transcriptome data of the Cancer Genome Atlas (TCGA) and Genotype\u2010Tissue Expression (GTEx) database, single\u2010cell and spatial transcriptome data of the Gene Expression Omnibus database (GEO), immunohistochemical data of the Human Protein Atlas (HPA) database and local LUAD to provide a scientific basis for precision treatment of LUAD. Secreted phosphoprotein\u20101 (SPP1) was identified as the central regulatory gene of LUAD. The single\u2010cell transcriptome data showed that SPP1 is up\u2010regulated in invasive lung carcinoma (ILC), while macrophage receptor with collagenous structure (MARCO) is up\u2010regulated in adenocarcinoma in\u00a0situ (AIS). MARCO\n                    <jats:sup>+<\/jats:sup>\n                    M2 macrophages and SPP1\n                    <jats:sup>+<\/jats:sup>\n                    M2 macrophages clustered in different positions in the uniform manifold approximation and projection (UMAP) to form mutually exclusive cell subsets. SPP1\n                    <jats:sup>+<\/jats:sup>\n                    M2 plays a major role in ILC and MARCO\n                    <jats:sup>+<\/jats:sup>\n                    M2 plays a major role in AIS. The spatial transcriptome data showed that some SPP1\n                    <jats:sup>+<\/jats:sup>\n                    M2 were clustered at the edge of the tumor, and this particular spatial location may increase tumor invasiveness. Further spatial distance analysis showed that the distance was greater from the SPP1\n                    <jats:sup>+<\/jats:sup>\n                    M2 to alveolar type 2 epithelial cell (AT2) than from the MARCO\n                    <jats:sup>+<\/jats:sup>\n                    M2. Immunohistochemical analysis showed that SPP1 expression was up\u2010regulated in the tumor or ILC group and notably higher in inflammatory cells. In summary, SPP1\n                    <jats:sup>+<\/jats:sup>\n                    M2 and MARCO\n                    <jats:sup>+<\/jats:sup>\n                    M2 form mutually exclusive cell subsets, and MARCO\n                    <jats:sup>+<\/jats:sup>\n                    M2 and SPP1\n                    <jats:sup>+<\/jats:sup>\n                    M2 synergistically promote different stages of tumor progression.\n                  <\/jats:p>","DOI":"10.1111\/cas.70247","type":"journal-article","created":{"date-parts":[[2025,11,22]],"date-time":"2025-11-22T07:51:23Z","timestamp":1763797883000},"page":"548-565","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Spatial Location of\n                    <scp>SPP1<\/scp>\n                    <sup>+<\/sup>\n                    <scp>TAMs<\/scp>\n                    and Mutually Exclusive Subsets Based on Single\u2010Cell and Transcriptome Data"],"prefix":"10.1111","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7838-2489","authenticated-orcid":false,"given":"Xuan","family":"Luo","sequence":"first","affiliation":[{"name":"Department of Pathology The First Affiliated Hospital of Kunming Medical University  Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JianGuo","family":"Xu","sequence":"additional","affiliation":[{"name":"Kunming Medical University School of Stomatology and Affiliated Stomatology Hospital  Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ZhiYuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology The First Affiliated Hospital of Kunming Medical University  Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"XiaoFang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology The First Affiliated Hospital of Kunming Medical University  Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"YangHao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology The First Affiliated Hospital of Kunming Medical University  Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathology The First Affiliated Hospital of Kunming Medical University  Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"FangFang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathology The First Affiliated Hospital of Kunming Medical University  Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Pathology The First Affiliated Hospital of Kunming Medical University  Kunming 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