{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T15:32:45Z","timestamp":1786116765925,"version":"build-2736575974"},"reference-count":31,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"vor","delay-in-days":217,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"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":["Stem Cells International"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Colon cancer (CC) remains a leading cause of cancer\u2010related mortality worldwide, driven largely by the complex interactions within the tumor microenvironment (TME). Fibroblast activation protein (FAP) is highly expressed in cancer\u2010associated fibroblasts (CAFs) and is associated with poor prognosis, yet its role in coordinating immune evasion and cancer stemness remains to be fully elucidated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We integrated multiomics data from TCGA and GEO databases, utilizing bulk RNA\u2010seq and single\u2010cell RNA\u2010seq (scRNA\u2010seq) analyses. Findings were validated via tissue microarray (TMA) immunohistochemistry (IHC). We further employed cell\u2013cell communication analysis, pseudotime trajectory modeling, and the Connectivity Map (CMap) for drug sensitivity prediction and molecular docking.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>FAP was significantly upregulated in CC tissues and correlated with advanced clinical stages. scRNA\u2010seq confirmed that FAP is predominantly expressed in CAFs. Functional analysis revealed that FAP\u2010high tumors are enriched in extracellular matrix (ECM) remodeling and immunosuppressive pathways. Cell\u2013cell communication analysis identified that FAP+\u2009CAFs interact with T cells and cancer stem cells (CSCs) primarily through the COL1A1\/2\u2010CD44 axis. Specifically, FAP+\u2009CAFs promote the differentiation of naive T cells into regulatory T cells (Tregs) and are positively correlated with various stemness markers, including CD44, ABCG2, and BMI1. Based on these findings, we established a 14\u2010gene prognostic risk model with robust predictive accuracy (area under the curve [AUC]\u2009&gt;\u20090.64) and identified AS604850 and LY364947 as potential therapeutic agents.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our study demonstrates that FAP+\u2009CAFs orchestrate a dual\u2010functional \u201cimmunosuppressive stem cell niche\u201d via the COL1A1\/2\u2010CD44 signaling axis. Targeting this FAP\u2010driven niche provides a promising strategy for overcoming immunotherapy resistance and improving clinical outcomes in CC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/sci\/4678145","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T11:59:02Z","timestamp":1786017542000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["FAP as a Clinical Biomarker: FAP+ CAFs Orchestrate an Immunosuppressive Stem Cell Niche via the COL1A1\/2\u2010CD44 Axis in Colon Cancer"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-7229-3858","authenticated-orcid":false,"given":"Qian","family":"Ding","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4636-9423","authenticated-orcid":false,"given":"Qingyan","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,6]]},"reference":[{"key":"e_1_2_11_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2023.102676"},{"key":"e_1_2_11_2_2","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21763"},{"key":"e_1_2_11_3_2","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.118.210435"},{"key":"e_1_2_11_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.18.7235"},{"key":"e_1_2_11_5_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-06-1746"},{"key":"e_1_2_11_6_2","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2019-319200"},{"key":"e_1_2_11_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.6363"},{"key":"e_1_2_11_8_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1183440"},{"key":"e_1_2_11_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-023-02806-3"},{"key":"e_1_2_11_10_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers16183158"},{"key":"e_1_2_11_11_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI181374"},{"key":"e_1_2_11_12_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.811485"},{"key":"e_1_2_11_13_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-020-01234-1"},{"key":"e_1_2_11_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1160062"},{"key":"e_1_2_11_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-006-0160-8"},{"key":"e_1_2_11_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature06306"},{"key":"e_1_2_11_17_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-0934"},{"key":"e_1_2_11_18_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI25947"},{"key":"e_1_2_11_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2250"},{"key":"e_1_2_11_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-023-06396-6"},{"key":"e_1_2_11_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2023.12.015"},{"key":"e_1_2_11_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3868"},{"key":"e_1_2_11_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4409"},{"key":"e_1_2_11_24_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-019-0994-2"},{"key":"e_1_2_11_25_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0703478104"},{"key":"e_1_2_11_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1004"},{"key":"e_1_2_11_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature06196"},{"key":"e_1_2_11_28_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18112362"},{"key":"e_1_2_11_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3418"},{"key":"e_1_2_11_30_2","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2022.1054152"},{"key":"e_1_2_11_31_2","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2026.5871"}],"container-title":["Stem 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