{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T05:50:31Z","timestamp":1784785831491,"version":"3.55.0"},"reference-count":52,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T00:00:00Z","timestamp":1771545600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T00:00:00Z","timestamp":1771545600000},"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":["82574138"],"award-info":[{"award-number":["82574138"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["92370133"],"award-info":[{"award-number":["92370133"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["iMetaOmics"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Disruption of proteostasis in the endoplasmic reticulum leads to the activation of the unfolded protein response (UPR). UPR activation is common in malignant cells and is often considered a contributor to cancer progression. However, the accurate evaluation of UPR status in pan\u2010cancer is still lacking. Furthermore, the UPR\u2010related key characteristics in cancer progression remain to be explored. To fill in these gaps, we first proposed a UPR signature, according to which a UPR score was assigned to each tumor\/tumor cell by gene set variation analysis. Based on this, we depicted the UPR landscape across 33 kinds of tumors and 28 kinds of normal tissues, which revealed significant inter\u2010 and intra\u2010tumoral heterogeneity in UPR activity across different cancers. Next, by integrating bulk and single\u2010cell transcriptomic data, we unveiled robust correlations of UPR activation with critical genomic and immune features amongst different cancers. In addition, by employing three machine learning algorithms, we identified and validated a promising biomarker derived from the perspective of UPR for breast cancer prognosis. In summary, our study offers an effective approach for evaluating UPR activity in human cancer and underscores the clinical significance of UPR activity in cancer progression.<\/jats:p>","DOI":"10.1002\/imo2.70084","type":"journal-article","created":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T01:16:39Z","timestamp":1771636599000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Comprehensive assessment of unfolded protein response and its association with tumor progression in pan\u2010cancer"],"prefix":"10.1002","volume":"3","author":[{"given":"Xinyu","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Urology, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan China"},{"name":"School of Public Health, Tongji Medical College Huazhong University of Science and Technology Wuhan China"},{"name":"Institute of Biomedical Research, School of Life and Health Sciences Hainan University Haikou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8238-3863","authenticated-orcid":false,"given":"Faming","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Urology, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan China"},{"name":"School of Public Health, Tongji Medical College Huazhong University of Science and Technology Wuhan China"},{"name":"Institute of Biomedical Research, School of Life and Health Sciences Hainan University Haikou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Research, School of Life and Health Sciences Hainan University Haikou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinran","family":"Xia","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Research, School of Life and Health Sciences Hainan University Haikou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liwei","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Research, School of Life and Health Sciences Hainan University Haikou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Zeng","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Research, School of Life and Health Sciences Hainan University Haikou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9720-7099","authenticated-orcid":false,"given":"Liang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Urology, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanxia","family":"Hu","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Research, School of Life and Health Sciences Hainan University Haikou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8742-7343","authenticated-orcid":false,"given":"Xia","family":"Sheng","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Research, School of Life and Health Sciences Hainan University Haikou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,20]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-015-2052-6"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2015.1091141"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2019.01.034"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-020-0250-z"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1515\/jtim-2025-0009"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-020-00312-2"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.02.034"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1209038"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3800"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature17041"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.01.076"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2020.07.006"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-08152-3"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202105469"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-024-02988-4"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201911845"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.750"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.711348"},{"key":"e_1_2_11_20_1","first-page":"1698","article-title":"A Human Pan\u2010Cancer System Analysis of Heat Shock Protein Family A Member 5","volume":"13","author":"Deng Chao","year":"2023","journal-title":"American Journal of Cancer Research"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.15252\/embr.202152509"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-019-0125-9"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.1064223"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.16321"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241814010"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506580102"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2016.36"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-017-0600-4"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1818210116"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-021-00911-1"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2022.04.008"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2016.03.007"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2022.10.010"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-023-04794-0"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/6655417"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-022-00963-8"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13119"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2021.114737"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0950-3552(98)80005-9"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20210564"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-022-04219-z"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202401061"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202500722"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.502"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1200282"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2024.1394585"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.596087"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0017238"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-14-7"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3337"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-019-0619-0"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1089\/omi.2011.0118"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21246-9"}],"container-title":["iMetaOmics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/imo2.70084","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/imo2.70084","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/imo2.70084","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T13:40:39Z","timestamp":1775828439000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/imo2.70084"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,20]]},"references-count":52,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["10.1002\/imo2.70084"],"URL":"https:\/\/doi.org\/10.1002\/imo2.70084","archive":["Portico"],"relation":{},"ISSN":["2996-9506","2996-9514"],"issn-type":[{"value":"2996-9506","type":"print"},{"value":"2996-9514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,20]]},"assertion":[{"value":"2025-11-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70084"}}