{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:23:23Z","timestamp":1760059403898,"version":"build-2065373602"},"reference-count":42,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T00:00:00Z","timestamp":1749600000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008363","name":"The Danish Cancer Society","doi-asserted-by":"publisher","award":["R269-A15841","L-2021-00163"],"award-info":[{"award-number":["R269-A15841","L-2021-00163"]}],"id":[{"id":"10.13039\/100008363","id-type":"DOI","asserted-by":"publisher"}]},{"name":"A.P. Moeller Foundation","award":["R269-A15841","L-2021-00163"],"award-info":[{"award-number":["R269-A15841","L-2021-00163"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Numerous clinical trials have attempted to improve first-line R-CHOP treatment of diffuse large B-cell lymphoma (DLBCL) through the addition or substitution of drugs. The REMoDL-B trial, testing the addition of bortezomib (RB-CHOP), revealed that ABC and molecular high-grade DLBCL patients benefit from bortezomib. The aim of this study was to achieve a better understanding of the bortezomib response in DLBCL through a functional investigation of clinically identified markers. A retrospective analysis of transcriptional and clinical data from the REMoDL-B trial was conducted to identify genes associated with bortezomib response, identifying CDCA2. DLBCL patients with high expression of CDCA2 had a superior survival outcome when treated with RB-CHOP in comparison to R-CHOP, whereas no difference in outcome was observed for patients with low CDCA2. Moreover, CDCA2 was found to be overexpressed in DLBCL compared to non-malignant tissue, and to have higher levels in GCB and MYC\/BCL2 double-expressor patients. Functional in vitro and in vivo studies revealed that knockout of CDCA2 decreased DLBCL cell proliferation and a bortezomib dose\u2013response analysis showed less sensitivity in CDCA2 knockout cells compared to control cells. This study shows that DLBCL patients with high CDCA2 expression benefitted from the addition of bortezomib to R-CHOP and functional studies documented a direct impact of CDCA2 on the bortezomib response in DLBCL cells.<\/jats:p>","DOI":"10.3390\/ijms26125596","type":"journal-article","created":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T11:18:40Z","timestamp":1749640720000},"page":"5596","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Overexpression of CDCA2 in Diffuse Large B-Cell Lymphoma Promotes Cell Proliferation and Bortezomib Sensitivity"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0567-9967","authenticated-orcid":false,"given":"Hanne","family":"Due","sequence":"first","affiliation":[{"name":"Department of Hematology, Clinical Cancer Research Center, Aalborg University Hospital, 9000 Aalborg, Denmark"},{"name":"Department of Clinical Medicine, Aalborg University, 9260 Gistrup, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4915-1970","authenticated-orcid":false,"given":"Asta","family":"Brogaard","sequence":"additional","affiliation":[{"name":"Department of Hematology, Clinical Cancer Research Center, Aalborg University Hospital, 9000 Aalborg, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0004-3030","authenticated-orcid":false,"given":"Issa Ismail","family":"Issa","sequence":"additional","affiliation":[{"name":"Department of Hematology, Clinical Cancer Research Center, Aalborg University Hospital, 9000 Aalborg, Denmark"},{"name":"Department of Clinical Medicine, Aalborg University, 9260 Gistrup, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2351-5676","authenticated-orcid":false,"given":"Maja Zimmer","family":"Jakobsen","sequence":"additional","affiliation":[{"name":"Department of Hematology, Clinical Cancer Research Center, Aalborg University Hospital, 9000 Aalborg, Denmark"},{"name":"Department of Clinical Medicine, Aalborg University, 9260 Gistrup, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5277-9434","authenticated-orcid":false,"given":"Cathrine","family":"Sylvester","sequence":"additional","affiliation":[{"name":"Department of Hematology, Clinical Cancer Research Center, Aalborg University Hospital, 9000 Aalborg, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne Krogh","family":"N\u00f8hr","sequence":"additional","affiliation":[{"name":"Center for Clinical Data Science, Aalborg University Hospital, and Aalborg University, 9260 Gistrup, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Louiza Bohn","family":"Thomsen","sequence":"additional","affiliation":[{"name":"Department of Health Science and Technology, Aalborg University, 9260 Gistrup, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5055-7531","authenticated-orcid":false,"given":"Martin Kristian","family":"Thomsen","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Aarhus University, 8000 Aarhus, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5537-6767","authenticated-orcid":false,"given":"Rasmus Froberg","family":"Br\u00f8ndum","sequence":"additional","affiliation":[{"name":"Center for Clinical Data Science, Aalborg University Hospital, and Aalborg University, 9260 Gistrup, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2488-435X","authenticated-orcid":false,"given":"Karen","family":"Dybk\u00e6r","sequence":"additional","affiliation":[{"name":"Department of Hematology, Clinical Cancer Research Center, Aalborg University Hospital, 9000 Aalborg, Denmark"},{"name":"Department of Clinical Medicine, Aalborg University, 9260 Gistrup, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1038\/35000501","article-title":"Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling","volume":"403","author":"Alizadeh","year":"2000","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1200\/JCO.2014.57.7080","article-title":"Diffuse large B-cell lymphoma classification system that associates normal B-cell subset phenotypes with prognosis","volume":"33","author":"Falgreen","year":"2015","journal-title":"J. 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