{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T18:56:39Z","timestamp":1781636199622,"version":"3.54.5"},"reference-count":44,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T00:00:00Z","timestamp":1776384000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T00:00:00Z","timestamp":1776384000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82271991"],"award-info":[{"award-number":["82271991"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Recent studies highlight the critical role of cancer\u2010associated fibroblasts (CAFs) in tumor invasion, but research on the regulation of\n                    <jats:italic>MFAP5<\/jats:italic>\n                    + fibroblasts by the pancreatic ductal adenocarcinoma (PDAC) tumor microenvironment (TME) remains limited. Therefore, understanding the function, spatial distribution, and communication dynamics of\n                    <jats:italic>MFAP5<\/jats:italic>\n                    + fibroblasts within the PDAC tumor microenvironment is essential. We used multi\u2010regional single\u2010cell RNA sequencing to examine the biological characteristics of\n                    <jats:italic>MFAP5<\/jats:italic>\n                    + fibroblasts in PDAC. A pseudo\u2010time analysis technique was then applied to infer the evolution of CAF subtypes. To investigate this functional role and spatial relationship, we employed multiplex immunofluorescence to observe the spatial distribution of\n                    <jats:italic>MFAP5<\/jats:italic>\n                    + fibroblasts and endothelial cells. Our study investigated PDAC tumor heterogeneity through a comprehensive analysis of 59,829 cells, which integrated our own multi\u2010regional sampling (GSE285264) with publicly available datasets (GSE277782, GSE155698, GSE212966). We found that\n                    <jats:italic>MFAP5<\/jats:italic>\n                    + fibroblasts were associated with\n                    <jats:italic>FABP4<\/jats:italic>\n                    + endothelial cells and\n                    <jats:italic>VWF<\/jats:italic>\n                    + endothelial cells via key tumor\u2010promoting pathways (e.g.,\n                    <jats:italic>TGF\u2010\u03b2<\/jats:italic>\n                    ,\n                    <jats:italic>VEGF<\/jats:italic>\n                    ,\n                    <jats:italic>FGF<\/jats:italic>\n                    ). Multiplex immunofluorescence and semi\u2010quantitative analysis confirmed increased prevalence of\n                    <jats:italic>FABP4<\/jats:italic>\n                    + and\n                    <jats:italic>VWF<\/jats:italic>\n                    + endothelial cells in areas with high\n                    <jats:italic>MFAP5<\/jats:italic>\n                    + fibroblast expression, along with elevated\n                    <jats:italic>VEGF<\/jats:italic>\n                    and\n                    <jats:italic>FGF<\/jats:italic>\n                    signaling. Our study reveals a potential pro\u2010tumorigenic mechanism of\n                    <jats:italic>MFAP5<\/jats:italic>\n                    + fibroblasts in PDAC, suggesting that the\n                    <jats:italic>MFAP5<\/jats:italic>\n                    + fibroblast\u2010endothelial cell axis may represent a potential target for future therapeutic strategies.\n                  <\/jats:p>","DOI":"10.1002\/mc.70114","type":"journal-article","created":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T14:16:32Z","timestamp":1776435392000},"page":"840-853","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Deciphering\n                    <i>MFAP5<\/i>\n                    + Fibroblasts in Pancreatic Cancer Progression via Multi\u2010Regional Single\u2010Cell RNA Sequencing With Experimental Validation"],"prefix":"10.1002","volume":"65","author":[{"given":"Wei","family":"Wei","sequence":"first","affiliation":[{"name":"Department of Radiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine University of Sciences and Technology of China Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0355-0832","authenticated-orcid":false,"given":"Wuyang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Radiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine University of Sciences and Technology of China Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Radiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine University of Sciences and Technology of China Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuyi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Radiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine University of Sciences and Technology of China Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Ming","sequence":"additional","affiliation":[{"name":"Department of Radiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine University of Sciences and Technology of China Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengru","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Radiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine University of Sciences and Technology of China Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Radiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine University of Sciences and Technology of China Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Radiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine University of Sciences and Technology of China Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Radiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine University of Sciences and Technology of China Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Radiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine University of Sciences and Technology of China Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Radiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine University of Sciences and Technology of China Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,17]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21763"},{"key":"e_1_2_12_3_1","doi-asserted-by":"crossref","unstructured":"T. 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