{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T21:00:45Z","timestamp":1791234045674,"version":"4.1.0"},"reference-count":39,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T00:00:00Z","timestamp":1757635200000},"content-version":"vor","delay-in-days":254,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Human Mutation"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Bladder urothelial carcinoma (BLCA) is a prevalent malignant tumor known for its high recurrence rates and limited therapeutic efficacy. Cellular senescence has been extensively shown to inhibit tumorigenesis via cell cycle arrest. Consequently, the identification of senescence\u2010associated biomarkers is essential for enhancing the diagnosis, prognosis, and immunotherapeutic outcomes of BLCA.<\/jats:p><jats:p><jats:bold>Method:<\/jats:bold> This study integrated the TCGA\u2010BLCA and GSE13507 datasets to analyze senescence\u2010related genes. ConsensusClusterPlus was employed for cluster analysis, while immune infiltration was assessed using CIBERSORT. A diagnostic and prognostic model for BLCA was developed and validated through the combination of various machine learning algorithms. Experimental validation was conducted using qRT\u2010PCR, colony formation, and Transwell assays to evaluate the functional role of PAQR4.<\/jats:p><jats:p><jats:bold>Result:<\/jats:bold> Our study revealed that aging\u2010related samples demonstrated improved survival rates and a lower incidence of high\u2010grade tumors. Cluster analysis identified two distinct subgroups of BLCA characterized by unique immune infiltration profiles and varying responses to immune checkpoint blockade. The diagnostic and prognostic models developed from aging\u2010related genes were subsequently validated. Notably, PAQR4 was identified as a critical aging\u2010related gene linked to poor prognosis and an immunosuppressive microenvironment. The knockdown of PAQR4 significantly inhibited the proliferation and metastasis of BLCA cells.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> PAQR4 is a novel biomarker and therapeutic target for BLCA, influencing cellular senescence, immune evasion, and metastasis. This study provides insights into the senescence\u2010related mechanisms and offers tools for precision diagnosis and the optimization of immunotherapy in BLCA.<\/jats:p>","DOI":"10.1155\/humu\/2227219","type":"journal-article","created":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T19:57:37Z","timestamp":1757707057000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["PAQR4: A Critical Senescence\u2010Related Gene Influencing Immune Evasion and Metastasis in Bladder Urothelial Carcinoma"],"prefix":"10.1155","volume":"2025","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-0447-7030","authenticated-orcid":false,"given":"Yizhang","family":"Sun","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xincheng","family":"Yi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenchao","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0341-0078","authenticated-orcid":false,"given":"Yuhua","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,12]]},"reference":[{"key":"e_1_2_11_1_2","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21763"},{"key":"e_1_2_11_2_2","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2022.1087246"},{"key":"e_1_2_11_3_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph14050508"},{"key":"e_1_2_11_4_2","doi-asserted-by":"publisher","DOI":"10.5489\/cuaj.777"},{"key":"e_1_2_11_5_2","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2018.9579"},{"key":"e_1_2_11_6_2","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2017.00278"},{"key":"e_1_2_11_7_2","doi-asserted-by":"publisher","DOI":"10.2174\/138161210789941874"},{"key":"e_1_2_11_8_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.722205"},{"key":"e_1_2_11_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2019.06.018"},{"key":"e_1_2_11_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2024.11.010"},{"key":"e_1_2_11_11_2","doi-asserted-by":"publisher","DOI":"10.1159\/000500683"},{"key":"e_1_2_11_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/jb\/mvaf001"},{"key":"e_1_2_11_13_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21124346"},{"key":"e_1_2_11_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0302-2838(24)00239-2"},{"key":"e_1_2_11_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10142-023-01163-4"},{"key":"e_1_2_11_16_2","doi-asserted-by":"publisher","DOI":"10.2174\/1389450120666181217100833"},{"key":"e_1_2_11_17_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms231911082"},{"key":"e_1_2_11_18_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.645593"},{"key":"e_1_2_11_19_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.210724"},{"key":"e_1_2_11_20_2","doi-asserted-by":"publisher","DOI":"10.1042\/BSR20171529"},{"key":"e_1_2_11_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2012.07.140"},{"key":"e_1_2_11_22_2","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2013.2077"},{"key":"e_1_2_11_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2017.1"},{"key":"e_1_2_11_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btq170"},{"key":"e_1_2_11_25_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-0327-7_16"},{"key":"e_1_2_11_26_2","doi-asserted-by":"publisher","DOI":"10.62347\/TECQ5002"},{"key":"e_1_2_11_27_2","doi-asserted-by":"publisher","DOI":"10.18632\/aging.204863"},{"key":"e_1_2_11_28_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-025-14109-9"},{"key":"e_1_2_11_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2022.175024"},{"key":"e_1_2_11_30_2","doi-asserted-by":"publisher","DOI":"10.1080\/08820139.2022.2118606"},{"key":"e_1_2_11_31_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj-2023-076743"},{"key":"e_1_2_11_32_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.908068"},{"key":"e_1_2_11_33_2","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.997702"},{"key":"e_1_2_11_34_2","doi-asserted-by":"publisher","DOI":"10.18632\/aging.204658"},{"key":"e_1_2_11_35_2","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.937951"},{"key":"e_1_2_11_36_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12672-024-00987-1"},{"key":"e_1_2_11_37_2","first-page":"701","article-title":"High PAQR4 mRNA Expression May Play a Key Role in Prognosis of Kidney Renal Papillary Cell Carcinoma","volume":"53","author":"Liu C.","year":"2023","journal-title":"Annals of Clinical and Laboratory Science"},{"key":"e_1_2_11_38_2","doi-asserted-by":"publisher","DOI":"10.1515\/biol-2022-0982"},{"key":"e_1_2_11_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2020.110223"}],"container-title":["Human Mutation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/humu\/2227219","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T19:57:38Z","timestamp":1757707058000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1155\/humu\/2227219"}},"subtitle":[],"editor":[{"given":"Minghua","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,1]]},"references-count":39,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,1]]}},"alternative-id":["10.1155\/humu\/2227219"],"URL":"https:\/\/doi.org\/10.1155\/humu\/2227219","archive":["Portico"],"relation":{},"ISSN":["1059-7794","1098-1004"],"issn-type":[{"value":"1059-7794","type":"print"},{"value":"1098-1004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1]]},"assertion":[{"value":"2025-05-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2227219"}}