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However, the mechanisms driving this transformation remain poorly understood. In this study, we employed a comprehensive multi\u2010omics approach, incorporating multiplex immunostaining and adeno\u2010associated virus (AAV)\u2010mediated mouse models, to systematically dissect the key drivers of malignant transformation in CRC. Our investigations revealed a dynamic and stage\u2010specific expression pattern of thrombospondin 2 (encoded by the gene\n                    <jats:italic>THBS2<\/jats:italic>\n                    ), characterized by significantly downregulated expression during the polyp stage, followed by markedly upregulated expression in malignant CRC tissues compared to healthy colon tissue. Intriguingly,\n                    <jats:italic>THBS2<\/jats:italic>\n                    expression was primarily localized within a distinct fibroblast subpopulation, with\n                    <jats:italic>THBS2<\/jats:italic>\n                    <jats:sup>+<\/jats:sup>\n                    fibroblasts exhibiting a tumor\u2010tropic infiltration pattern. Through a series of analyses, we hypothesized that\n                    <jats:italic>THBS2<\/jats:italic>\n                    <jats:sup>+<\/jats:sup>\n                    fibroblasts may play a role in coordinating CRC progression via the THBS2\u2013CD36 and THBS2\u2013SDC1 pathways. Furthermore, depletion of\n                    <jats:italic>THBS2<\/jats:italic>\n                    <jats:sup>+<\/jats:sup>\n                    fibroblasts enhanced polyp formation but suppressed tumor formation in a thymidine kinase 1\/ganciclovir\/azoxymethane\/dextran sulfate sodium mouse model. The comprehensive multi\u2010omics atlas and complementary data presented here will advance our understanding of the mechanisms underlying CRC malignant transformation and may provide a potential therapeutic target. \u00a9 2026 The Pathological Society of Great Britain and Ireland.\n                  <\/jats:p>","DOI":"10.1002\/path.70026","type":"journal-article","created":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T08:30:24Z","timestamp":1770280224000},"page":"445-459","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Roles of\n                    <scp>\n                      <i>THBS2<\/i>\n                    <\/scp>\n                    <sup>+<\/sup>\n                    fibroblasts in malignant transformation of colorectal polyp to cancer"],"prefix":"10.1002","volume":"268","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-7250-948X","authenticated-orcid":false,"given":"Qizheng","family":"Han","sequence":"first","affiliation":[{"name":"Department of Pathology and International Institutes of Medicine, The Fourth Affiliated Hospital (Yiwu) Zhejiang University School of Medicine  Hangzhou PR China"},{"name":"Research Unit of Intelligence Classification of Tumor Pathology and Precision Therapy Chinese Academy of Medical Sciences (2019RU042)  Hangzhou PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathology and International Institutes of Medicine, The Fourth Affiliated Hospital (Yiwu) Zhejiang University School of Medicine  Hangzhou PR China"},{"name":"Research Unit of Intelligence Classification of Tumor Pathology and Precision Therapy Chinese Academy of Medical Sciences (2019RU042)  Hangzhou PR 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