{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T19:37:07Z","timestamp":1786390627941,"version":"build-2736575974"},"reference-count":32,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Vet Comparative Oncology"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Rational, mechanism\u2010based drug selection for canine diffuse large B\u2010cell lymphoma (DLBCL) remains limited, despite extensive molecular work in human DLBCL. We asked whether human and canine DLBCL share a conserved transcriptional network that could anchor therapeutic hypotheses for dogs. Using public human and canine DLBCL transcriptomes, we derived a 409\u2010gene cross\u2010species module defined by concordant tumour\u2013normal dysregulation and projected it onto pathway and protein\u2013protein interaction (PPI) networks. The module was dominated by DNA replication, cell\u2010cycle checkpoint and DNA damage\u2013response programmes and contained a compact PPI core centred on TOP2A and PARP1. Querying the Connectivity Map\/LINCS library with the human component of the module highlighted anthracycline\u2010like topoisomerase II poisons (valrubicin, etoposide, amsacrine) and the PARP inhibitor rucaparib among the ~0.2% most negative connectivity scores, while directly targeting TOP2A and\/or PARP1. A simple up\u2013down module score strongly separated tumour from normal lymph nodes in both species and was associated with outcome: higher scores predicted longer progression\u2010free survival in CHOP\u2010treated dogs and better overall survival in an independent human cohort, with a similar but underpowered trend in TCGA\u2010DLBC. Finally, extracellular\u2010vesicle microRNA (EV\u2010miRNA) profiling in human DLBCL showed that differentially expressed EV\u2010miRNAs, including let\u20107 family members, miR\u201021\u20105p, miR\u2010124\u20103p and miR\u2010205\u20105p, converge on the same TOP2A\/PARP1\u2010centred core. These cross\u2010species, multi\u2010layer data support topoisomerase II poisons and PARP inhibition as coherent, network\u2010anchored candidate therapies for canine DLBCL, with module scores and EV\u2010miRNAs as candidate biomarkers.<\/jats:p>","DOI":"10.1111\/vco.70079","type":"journal-article","created":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T04:53:37Z","timestamp":1779339217000},"page":"578-592","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cross\u2010Species Transcriptomic and Network Analysis of Human and Canine Diffuse Large B\u2010Cell Lymphoma Identifies a Conserved Replication\u2013\n                    <scp>DNA<\/scp>\n                    Damage Module for Drug Repurposing"],"prefix":"10.1111","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-5349-4997","authenticated-orcid":false,"given":"Soroush","family":"Akbari\u2010Ardabili","sequence":"first","affiliation":[{"name":"Department of Basic Sciences, Faculty of Veterinary Medicine Urmia University  Urmia Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8809-2805","authenticated-orcid":false,"given":"Safiyeh","family":"Aghazadeh","sequence":"additional","affiliation":[{"name":"Department of Basic Sciences, Faculty of Veterinary Medicine Urmia University  Urmia 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