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Here, we integrate spatial transcriptomics, single\u2010cell RNA sequencing, and single\u2010cell DNA sequencing on coexisting DCIS and IDC samples to characterize cellular and microenvironmental alterations. Integrated analyses reveal differential molecular characterizations between coexisting DCIS and IDC and identify candidate genes (\n                    <jats:italic>MGP<\/jats:italic>\n                    ,\n                    <jats:italic>PLAT<\/jats:italic>\n                    , and\n                    <jats:italic>SERPINA3<\/jats:italic>\n                    ) potentially limiting the progression from DCIS to IDC. Malignant epithelial meta\u2010programs (MPs) delineate distinct transcriptional states, with development\u2010associated MP1 enriched in DCIS and cell cycle\u2010related MP5 enriched in IDC. Further analysis reveals varied microenvironmental features in DCIS and IDC, with invasion\u2010associated Mph_SPP1 and development\u2010associated iCAFs_HOPX enriched in DCIS, while immunosuppressive Mph_PRDM1 and metabolism\u2010related tCAFs_BNIP3 predominate in IDC. We then construct a machine learning model to identify DCIS at high risk of progression, which is externally validated across independent bulk RNA\u2010sequencing cohorts (mean AUC = 0.903). Collectively, this study provides an integrative framework for understanding the molecular and spatial features that distinguish DCIS from IDC, with the potential to inform more precise risk stratification and clinical management for DCIS progression.\n                  <\/jats:p>","DOI":"10.1002\/advs.77897","type":"journal-article","created":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T18:00:31Z","timestamp":1790532031000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated Multi\u2010Omics Reveals Cellular States and Microenvironmental Remodeling in Coexisting DCIS and IDC"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6430-4236","authenticated-orcid":false,"given":"Ning","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Breast Surgery General Surgery Qilu Hospital of Shandong University  Ji'nan 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