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In this study, we integrated single\u2010cell RNA sequencing and spatial transcriptomic data from CRC tissues to examine cancer\u2010associated fibroblast (CAF)\u2010dominant spatial domains. GPC1 and CHPF were enriched in stromal regions and showed higher expression in CRC tissues than in normal tissues. In the analyzed cohorts, higher GPC1 and CHPF expression was associated with advanced clinicopathological features and poorer survival outcomes in univariate analyses. Single\u2010cell analyses showed that GPC1 and CHPF were mainly expressed in fibroblasts and were enriched in an ADAM12\u2010associated fibroblast subset with myofibroblast\u2010like features, extracellular matrix\u2010related genes, and hypoxia\/glycolysis\u2010related signatures. Cell\u2013cell communication analysis suggested that this fibroblast subset was linked to higher inferred WNT signaling. Drug\u2010response and immunotherapy\u2010related analyses further showed that GPC1 and CHPF expression was associated with transcriptomic patterns related to treatment response. In mucinous adenocarcinoma (MA), the ADAM12\u2010associated fibroblast program showed stronger inferred MIF\u2010related signaling and was associated with macrophage M2\u2010like features. Spatial mapping and multiplex immunofluorescence supported partial colocalization of GPC1, CHPF, and ADAM12 in CAF\u2010rich stromal regions. In CAFs, GPC1 or CHPF knockdown reduced ADAM12, CAF activation markers, and WNT\/MIF\u2010related proteins, while ADAM12 knockdown weakened macrophage M2\u2010like marker expression in a co\u2010culture model. These findings suggest that GPC1 and CHPF mark an ADAM12\u2010associated CAF program linked to stromal remodeling and immune\u2010related features in CRC, especially in MA, but further studies are needed to define its functional role.<\/jats:p>","DOI":"10.1002\/cam4.72369","type":"journal-article","created":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T04:37:48Z","timestamp":1791866268000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated\n                    <scp>scRNA<\/scp>\n                    \u2010Seq and Spatial Transcriptomics Reveal\n                    <scp>CHPF<\/scp>\n                    and\n                    <scp>GPC1<\/scp>\n                    as Markers of Cancer\u2010Associated Fibroblast\u2013Dominant Domains in Colorectal 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