{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T03:39:22Z","timestamp":1777865962675,"version":"3.51.4"},"reference-count":48,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"vor","delay-in-days":119,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100014895","name":"Southwest Medical University","doi-asserted-by":"publisher","award":["S202410632176"],"award-info":[{"award-number":["S202410632176"]}],"id":[{"id":"10.13039\/501100014895","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014895","name":"Southwest Medical University","doi-asserted-by":"publisher","award":["YCZD2024-298"],"award-info":[{"award-number":["YCZD2024-298"]}],"id":[{"id":"10.13039\/501100014895","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Human Mutation"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy characterized by a complex tumor microenvironment. Ubiquitination regulates key oncogenic processes and microenvironmental remodeling; however, its cell type\u2013specific activity and spatial organization within the PDAC microenvironment remain poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>Single\u2010cell RNA sequencing, spatial transcriptomics, and bulk RNA\u2010seq datasets of PDAC were integrated for multiomics analysis. Ubiquitination activity was quantified using gene\u2010set scoring algorithms, followed by cell\u2010communication and spatial interaction analyses. Prognostic models were constructed using bulk cohorts, and key findings were validated through gene\u2010silencing functional assays.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Ubiquitination activity was significantly increased in PDAC tissues compared with adjacent normal tissues, with ductal epithelial cells and fibroblasts showing the most prominent elevation. High ubiquitination states were associated with enhanced ductal\u2013fibroblast interactions and distinct spatial patterns linked to invasion\u2010associated tumor regions. Integration of ubiquitination\u2010associated gene signatures identified a robust prognostic model, highlighting an extracellular matrix\u2013related factor consistently overexpressed in tumors and associated with poor survival. Functional assays demonstrated that suppression of this factor inhibited proliferation, migration, invasion, and survival of pancreatic cancer cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Ubiquitination organizes ductal\u2013fibroblast crosstalk within the PDAC microenvironment and links spatial tumor ecology with disease aggressiveness and patient prognosis. Targeting ubiquitination\u2010associated microenvironmental programs may offer new strategies for prognostic stratification and therapeutic intervention.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/humu\/1665552","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T07:45:46Z","timestamp":1777535146000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ubiquitination\u2010Associated Ductal\u2013Fibroblast Crosstalk Shapes Tumor Progression and Prognosis in Pancreatic Ductal Adenocarcinoma"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-7782-1507","authenticated-orcid":false,"given":"Yiping","family":"Fu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-4274-9973","authenticated-orcid":false,"given":"Xin","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4254-9338","authenticated-orcid":false,"given":"Lai","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9512-8739","authenticated-orcid":false,"given":"Shengke","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8145-0199","authenticated-orcid":false,"given":"Yuheng","family":"Gu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5987-7048","authenticated-orcid":false,"given":"Ziye","family":"Zhuang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4679-1766","authenticated-orcid":false,"given":"Gang","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhulin","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2293-6917","authenticated-orcid":false,"given":"Pei","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5831-2491","authenticated-orcid":false,"given":"Xiaolin","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,4,30]]},"reference":[{"key":"e_1_2_10_1_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2019.01.259"},{"key":"e_1_2_10_2_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2023.02.012"},{"key":"e_1_2_10_3_2","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2015.64.0730"},{"key":"e_1_2_10_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2016.22"},{"key":"e_1_2_10_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1062-1"},{"key":"e_1_2_10_6_2","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21387"},{"key":"e_1_2_10_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-020-0107-0"},{"key":"e_1_2_10_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3739"},{"key":"e_1_2_10_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb3358"},{"key":"e_1_2_10_10_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-020-01262-x"},{"key":"e_1_2_10_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-020-01527-1"},{"key":"e_1_2_10_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-29684-9"},{"key":"e_1_2_10_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3192"},{"key":"e_1_2_10_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.04.048"},{"key":"e_1_2_10_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cels.2019.03.003"},{"key":"e_1_2_10_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-019-0619-0"},{"key":"e_1_2_10_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4463"},{"key":"e_1_2_10_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.csbj.2021.06.043"},{"key":"e_1_2_10_19_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12859-018-2435-4"},{"key":"e_1_2_10_20_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-14-7"},{"key":"e_1_2_10_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21246-9"},{"key":"e_1_2_10_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.xinn.2021.100141"},{"key":"e_1_2_10_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac963"},{"key":"e_1_2_10_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-020-00795-2"},{"key":"e_1_2_10_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3192"},{"key":"e_1_2_10_26_2","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.Cd-21-0316"},{"key":"e_1_2_10_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-021-00830-w"},{"key":"e_1_2_10_28_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkae267"},{"key":"e_1_2_10_29_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-022-02663-5"},{"key":"e_1_2_10_30_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab043"},{"key":"e_1_2_10_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2859"},{"key":"e_1_2_10_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4150"},{"key":"e_1_2_10_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4402"},{"key":"e_1_2_10_34_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"e_1_2_10_35_2","doi-asserted-by":"publisher","DOI":"10.1186\/cc2955"},{"key":"e_1_2_10_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/75556"},{"key":"e_1_2_10_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.4314"},{"key":"e_1_2_10_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-019-0143-7"},{"key":"e_1_2_10_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3845"},{"key":"e_1_2_10_40_2","doi-asserted-by":"publisher","DOI":"10.1186\/1476-4598-12-152"},{"key":"e_1_2_10_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2013"},{"key":"e_1_2_10_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2020.107753"},{"key":"e_1_2_10_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-021-00546-5"},{"key":"e_1_2_10_44_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00048.2019"},{"key":"e_1_2_10_45_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12935-024-03563-3"},{"key":"e_1_2_10_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-018-0276-y"},{"key":"e_1_2_10_47_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-40271-4"},{"key":"e_1_2_10_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2018.03.023"}],"container-title":["Human Mutation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/humu\/1665552","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1155\/humu\/1665552","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/humu\/1665552","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T07:45:48Z","timestamp":1777535148000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1155\/humu\/1665552"}},"subtitle":[],"editor":[{"given":"Shaoqiu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":48,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1155\/humu\/1665552"],"URL":"https:\/\/doi.org\/10.1155\/humu\/1665552","archive":["Portico"],"relation":{},"ISSN":["1059-7794","1098-1004"],"issn-type":[{"value":"1059-7794","type":"print"},{"value":"1098-1004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"2026-01-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-30","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"1665552"}}