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Building on the growing emphasis on extracellular matrix (ECM) changes in cancer progression, the study tested how ECM proteomes differ spatially between DCIS and IBC. Multiplexed spatial proteomics of pathologically annotated tissue sections detected 1,005 ECM peptides, identifying 43 significantly altered peptides and collagen signatures that distinguish DCIS from IBC with high specificity and sensitivity. Imaging also revealed DCIS lesion microenvironment heterogeneity and an invasive cancer field effect in which nearby DCIS lesions shared more similar ECM profiles with IBC.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/extracellular-microenvironment-alterations-in-ductal-carcinoma-in-situ-and-invasive-breast-cancer-pathologies-by-multiplexed-spatial-proteomics/328239/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/extracellular-microenvironment-alterations-in-ductal-carcinoma-in-situ-and-invasive-breast-cancer-pathologies-by-multiplexed-spatial-proteomics/328239.png","ImageObject",300,407,{"name":92,"@type":93},"Maeve","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-01","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",11,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What is the study investigating about DCIS and IBC?","Question",{"text":113,"@type":114},"It investigates how extracellular matrix (ECM) proteomes change in ductal carcinoma in situ (DCIS) compared with invasive breast cancer (IBC), including spatial regulation relevant to disease progression.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How was the ECM proteome measured?",{"text":118,"@type":114},"Tissue sections with detailed pathological annotations were analyzed using multiplexed spatial proteomics, with lesion-targeted proteomic imaging to assess spatial heterogeneity.",{"name":120,"@type":111,"acceptedAnswer":121},"What findings distinguish DCIS from IBC?",{"text":122,"@type":114},"A comparison between DCIS and IBC showed 43 significantly altered ECM peptides, and eight fibrillar collagen peptides provided high specificity and sensitivity to distinguish the two pathologies.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},328239,1790013106,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":146,"preview_page_count":4},5909877438554,"https://ap-avatar.wpscdn.com/avatar/5600025385ad2bf12a7?_k=1778553567797529272","Article  \nExtracellular Microenvironment Alterations in Ductal Carcinoma In Situ and Invasive Breast Cancer Pathologies by Multiplexed Spatial Proteomics  \nTaylor S. Hulahan 1, Laura Spruill 2, Elizabeth N. Wallace 1, Yeonhee Park 3, Robert B. West 4, Jeffrey R. Marks 5, E. Shelley Hwang 5, Richard R. Drake 1 and Peggi M. Angel 1, *  \nCitation: Hulahan, T.S.; Spruill, L.; Wallace, E.N.; Park, Y.; West, R.B.; Marks, J.R.; Hwang, E.S.; Drake, R.R.; Angel, P.M. Extracellular Microenvironment Alterations in Ductal Carcinoma In Situ and Invasive Breast Cancer Pathologies by Multiplexed Spatial Proteomics. Int. J. Mol. Sci. 2024, 25, 6748. [https://](https://)[ ](https://)[doi.org/10.3390/ijms25126748](doi.org/10.3390/ijms25126748)  \nAcademic Editor: Davide Raineri  \nReceived: 7 May 2024  \nRevised: 10 June 2024  \nAccepted: 16 June 2024  \nPublished: 19 June 2024  \nCopyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, SC 29425, USA; [hulahan@musc.edu](hulahan@musc.edu) (T.S.H.); [wallaeli@musc.edu](wallaeli@musc.edu) (E.N.W.); [draker@musc.edu](draker@musc.edu) (R.R.D.)  \n2 Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC 29425, USA; [spruill@musc.edu](spruill@musc.edu)  \n3 Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, WI 53726, USA; [ypark56@wisc.edu](ypark56@wisc.edu)  \n4 Department of Pathology Clinical, Stanford University, Stanford, CA 94305, USA; [rbwest@stanford.edu](rbwest@stanford.edu)  \n5 Department of Surgery, Duke University, Durham, NC 27710, USA; [jeffrey.marks@duke.edu](jeffrey.marks@duke.edu) (J.R.M.); [shelley.hwang@duke.edu](shelley.hwang@duke.edu) (E.S.H.)  \n* Correspondence: [angelp@musc.edu](angelp@musc.edu)  \nAbstract: Ductal carcinoma in situ (DCIS) is a heterogeneous breast disease that remains challenging to treat due to its unpredictable progression to invasive breast cancer (IBC) . Contemporary literature has become increasingly focused on extracellular matrix (ECM) alterations with breast cancer progression. However, the spatial regulation of the ECM proteome in DCIS has yet to be investigated in relation to IBC. We hypothesized that DCIS and IBC present distinct ECM proteomes that could discriminate between these pathologies. Tissue sections of pure DCIS, mixed DCIS-IBC, or pure IBC (n = 22) with detailed pathological annotations were investigated by multiplexed spatial proteomics. Across tissues, 1,005 ECM peptides were detected in pathologically annotated regions and their surrounding extracellular microenvironments. A comparison of DCIS to IBC pathologies demonstrated 43 significantly altered ECM peptides. Notably, eight fibrillar collagen peptides could distinguish with high specificity and sensitivity between DCIS and IBC. Lesion-targeted proteomic imaging revealed heterogeneity of the ECM proteome surrounding individual DCIS lesions. Multiplexed spatial proteomics reported an invasive cancer field effect, in which DCIS lesions in closer proximity to IBC shared a more similar ECM profile to IBC than distal counterparts. Defining the ECM proteomic microenvironment provides novel molecular insights relating to DCIS and IBC.  \nKeywords: extracellular matrix (ECM); tumor microenvironment; ductal carcinoma in situ (DCIS); invasive ductal carcinoma (IDC); invasive breast cancer (IBC); collagen; matrix-assisted laser desorption/ ionization–mass spectrometry imaging (MALDI-MSI)  \n1. Introduction  \nDuctal carcinoma in situ (DCIS) represents approximately 20% of breast cancers current","cbCaikhinaiUakQ1","https://ap.wps.com/l/cbCaikhinaiUakQ1","pdf",4953503,21,"English","# Introduction\n## Study background and clinical challenge\n## Need for improved biological markers","[{\"question\":\"What is the study investigating about DCIS and IBC?\",\"answer\":\"It investigates how extracellular matrix (ECM) proteomes change in ductal carcinoma in situ (DCIS) compared with invasive breast cancer (IBC), including spatial regulation relevant to disease progression.\"},{\"question\":\"How was the ECM proteome measured?\",\"answer\":\"Tissue sections with detailed pathological annotations were analyzed using multiplexed spatial proteomics, with lesion-targeted proteomic imaging to assess spatial heterogeneity.\"},{\"question\":\"What findings distinguish DCIS from IBC?\",\"answer\":\"A comparison between DCIS and IBC showed 43 significantly altered ECM peptides, and eight fibrillar collagen peptides provided high specificity and sensitivity to distinguish the two pathologies.\"}]","Extracellular Microenvironment Alterations in Ductal Carcinoma In Situ and Invasive Breast Cancer Pathologies by Multiplexed Spatial Proteomics | PDF",1789979016,53]