{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T16:08:18Z","timestamp":1791216498130,"version":"4.1.0"},"reference-count":57,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T00:00:00Z","timestamp":1749686400000},"content-version":"vor","delay-in-days":162,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82203428"],"award-info":[{"award-number":["82203428"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"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> The apoptosis affected the prostate adenocarcinoma (PRAD); we aimed to explore the potential pathogenesis of high\u2010risk patients based on the apoptosis features.<\/jats:p><jats:p><jats:bold>Method:<\/jats:bold> The RNA\u2010seq data of patients and apoptosis genes were used for apoptosis score calculation via \u201cGSVA\u201d package; then, the weighted gene coexpression network analysis (WGCNA) and Lasso algorithm were performed for a RiskScore model. After that, the \u201cmaftools\u201d package was applied for the somatic mutation analysis. By combining the Kaplan\u2013Meier (KM) survival curves in order to compare the prognosis of different subgroups of patients, Cell Counting Kit\u20108 (CCK\u20108), EdU staining, and Transwell assays were performed. Protein expression was measured using western blotting. Finally, the activity of PRAD cells in macrophage polarization was detected using coculture and immunofluorescence assays.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> The PRAD samples had significantly lower apoptosis scores, and the RiskScore supported the risk stratification of patients. In somatic mutation analysis, <jats:italic>EPHB1<\/jats:italic> and <jats:italic>KIF13A<\/jats:italic> from the top six mutant genes were overexpressed in 22RV1 and PC\u20103 tumor cells, and low levels of <jats:italic>EPHB1<\/jats:italic> indicated a better prognosis. Overexpression or knockdown of <jats:italic>EPHB1<\/jats:italic> affected cell viability, proliferation, and invasion. We found that high expression of <jats:italic>EPHB1<\/jats:italic> interacting with GSK3B protein promoted the expression of <jats:italic>p-SMAD3<\/jats:italic> in 22RV1 cells with high levels of antiapoptotic and invasion markers (<jats:italic>BCL2<\/jats:italic>, <jats:italic>Snail<\/jats:italic>, and <jats:italic>N-CAD<\/jats:italic>). Importantly, <jats:italic>GSK3B<\/jats:italic> and <jats:italic>EPHB1<\/jats:italic> knockdown inhibited <jats:italic>p-SMAD3<\/jats:italic> activation and promoted proapoptotic features, accompanied by a reduction in macrophage M2 polarization.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> This study revealed that <jats:italic>EPHB1<\/jats:italic> plays a pivotal role in activating the EPHB1\u2010GSK3B\u2010SMAD3 pathway to facilitate PRAD progression.<\/jats:p>","DOI":"10.1155\/humu\/4961883","type":"journal-article","created":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T15:17:50Z","timestamp":1749741470000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["EPHB1 Protein Promoted the Progression of Prostate Adenocarcinoma Through Phosphorylating GSK3B and Activating EPHB1\u2010GSK3B\u2010SMAD3 Pathway"],"prefix":"10.1155","volume":"2025","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-7054-5021","authenticated-orcid":false,"given":"Bohan","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8332-9946","authenticated-orcid":false,"given":"Shen","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1542-6437","authenticated-orcid":false,"given":"Kai","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,12]]},"reference":[{"key":"e_1_2_15_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-020-00613-6"},{"key":"e_1_2_15_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.12342"},{"key":"e_1_2_15_3_2","doi-asserted-by":"publisher","DOI":"10.3389\/fsurg.2022.856446"},{"key":"e_1_2_15_4_2","doi-asserted-by":"publisher","DOI":"10.1590\/S1677-5538.IBJU.2016.0483"},{"key":"e_1_2_15_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2018.08.033"},{"key":"e_1_2_15_6_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2018.0587"},{"key":"e_1_2_15_7_2","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27175730"},{"key":"e_1_2_15_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)00950-8"},{"key":"e_1_2_15_9_2","doi-asserted-by":"publisher","DOI":"10.32604\/oncologie.2022.026248"},{"key":"e_1_2_15_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.10.033"},{"key":"e_1_2_15_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.02.013"},{"key":"e_1_2_15_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0908428107"},{"key":"e_1_2_15_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2014.05.002"},{"key":"e_1_2_15_14_2","first-page":"4438","article-title":"Overexpression of Bcl-2 Protects Prostate Cancer Cells From Apoptosis In Vitro and Confers Resistance to Androgen Depletion In Vivo","volume":"55","author":"Raffo A. 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