{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T02:13:22Z","timestamp":1789524802189,"version":"build-2803163510"},"reference-count":48,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T00:00:00Z","timestamp":1749600000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","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":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy; however, no validated treatments are currently available. Clinically, the tumor position, head and uncinate process (HU), or body and tail (BT) of the pancreas are vital for surgical strategies; however, fundamental research has seldom revealed the heterogeneous tumor microenvironment (TME) among different types of PDAC. Here, we applied multicohort single\u2010cell and spatial RNA\u2010seq methods together with patient\u2010derived organoid models to reveal the TME heterogeneity between HU and BT PDAC. Osteopontin, encoded by <jats:italic>SPP1<\/jats:italic>, is secreted by vessel endothelial cells in BT PDAC and is associated with increased tumor burden. The number of tumor cells marked by CRABP2 was lower in BT PDAC and was identified as a prognostic marker of overall survival, as well as CD8<jats:sup>+<\/jats:sup> T\u2010cell infiltration. The expression of <jats:italic>CRABP2<\/jats:italic> was also validated to be downregulated in BT PDAC in patient\u2010derived organoid models. Overall, we profiled the heterogeneous PDAC TME between HU and BT PDAC, which could provide novel insight into the relationships between clinical characteristics and TME molecular research.<\/jats:p>","DOI":"10.1002\/mc.23936","type":"journal-article","created":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T18:23:02Z","timestamp":1749666182000},"page":"1379-1393","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["SPP1<sup>+<\/sup> Venous Endothelial Cells and CRABP2<sup>+<\/sup> Tumor Cells Contribute to Favorable Body and Tail Pancreatic Ductal Adenocarcinoma Tumor Microenvironment"],"prefix":"10.1002","volume":"64","author":[{"given":"Yueze","family":"Liu","sequence":"first","affiliation":[{"name":"General Surgery Department, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1678-6338","authenticated-orcid":false,"given":"Yifan","family":"Fu","sequence":"additional","affiliation":[{"name":"General Surgery Department, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"},{"name":"4+4 Medical Doctor Program Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Liu","sequence":"additional","affiliation":[{"name":"General Surgery Department, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology, State Key Laboratory of Complex Severe and Rare Disease Molecular Pathology Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"General Surgery Department, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanan","family":"Shi","sequence":"additional","affiliation":[{"name":"Medical Research Center, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Cao","sequence":"additional","affiliation":[{"name":"General Surgery Department, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Yang","sequence":"additional","affiliation":[{"name":"General Surgery Department, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Chen","sequence":"additional","affiliation":[{"name":"General Surgery Department, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9914-5338","authenticated-orcid":false,"given":"Wenhao","family":"Luo","sequence":"additional","affiliation":[{"name":"General Surgery Department, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinxin","family":"Tao","sequence":"additional","affiliation":[{"name":"General Surgery Department, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyang","family":"Wang","sequence":"additional","affiliation":[{"name":"General Surgery Department, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guihu","family":"Weng","sequence":"additional","affiliation":[{"name":"General Surgery Department, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menggang","family":"Zhang","sequence":"additional","affiliation":[{"name":"General Surgery Department, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liyuan","family":"Ye","sequence":"additional","affiliation":[{"name":"General Surgery Department, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianchun","family":"Xiao","sequence":"additional","affiliation":[{"name":"General Surgery Department, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangdong","family":"Qiu","sequence":"additional","affiliation":[{"name":"General Surgery Department, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taiping","family":"Zhang","sequence":"additional","affiliation":[{"name":"General Surgery Department, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Huang","sequence":"additional","affiliation":[{"name":"General Surgery Department, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,11]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.02.014"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-23731-7"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20190354"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2019.1588"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-019-0195-y"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2021.03.006"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2023.12.002"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.Cd-19-0094"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3398"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2023.05.036"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-024-01914-4"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(13)61903-0"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(24)02226-8"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2024.217193"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.24.00393"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0088-0"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamasurg.2019.5047"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1080\/0284186x.2018.1518593"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/bjs.10772"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2018.10.008"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41698-024-00571-4"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.16281"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-022-09279-9"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2020.100715"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.Cd-19-0597"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-019-0619-0"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-020-0591-3"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21246-9"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-020-00795-2"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xinn.2021.100141"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-14-7"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0694-x"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz430"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-40727-7"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06685-2"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-024-02050-7"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07698-1"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41698-024-00586-x"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/d41573-022-00030-4"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2024.101589"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-022-00579-0"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-023-00856-2"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2021.08.023"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2022.02.002"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1042\/bcj20160613"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2020.07.046"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.124.325458"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-023-06398-4"}],"container-title":["Molecular Carcinogenesis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mc.23936","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T12:46:59Z","timestamp":1753447619000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mc.23936"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,11]]},"references-count":48,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2025,8]]}},"alternative-id":["10.1002\/mc.23936"],"URL":"https:\/\/doi.org\/10.1002\/mc.23936","archive":["Portico"],"relation":{},"ISSN":["0899-1987","1098-2744"],"issn-type":[{"value":"0899-1987","type":"print"},{"value":"1098-2744","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,11]]},"assertion":[{"value":"2025-03-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-26","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}