{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T01:53:24Z","timestamp":1791338004203,"version":"4.3.1"},"reference-count":61,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T00:00:00Z","timestamp":1770681600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T00:00:00Z","timestamp":1770681600000},"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":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Canine hepatocellular carcinoma (HCC) requires further molecular characterization to identify diagnostic and therapeutic targets, and to establish whether dogs with this condition can model the human disease. Accordingly, we aimed to identify differentially expressed genes (DEGs) in canine HCC and evaluate cross\u2010species transcriptomic dysregulation in canine and human HCC. Liver tissue samples from three dogs with HCC and three healthy dogs were subjected to next\u2010generation sequencing, followed by RT\u2010qPCR validation. Identified DEGs were then targeted in bioinformatics analyses (pathway enrichment, protein\u2010protein interaction network, and hub gene analyses) for molecular characterization and comparison with human HCC datasets. We identified 975 DEGs (upregulated: 604; and downregulated: 371). Extracellular matrix\u2010receptor interaction, focal adhesion, cell adhesion molecule, PI3K\/Akt signaling, and cytokine\/chemokine\u2010related pathways were enriched. C1R, APOC3, C1QA, APOA1, C1QB, ACTG1, C1QC, CRP, ANXA5, and ANXA2 were identified as hub genes. Canine and human HCCs share 118 DEGs, highlighting conserved alterations in metabolic pathways, PI3K\u2010Akt signaling, focal adhesion, and PPAR signaling pathways. Based on human HCC data, SPP1, NQO1, RRM2, APOA1, APOC3, ALDOB, and IGF1 were identified as prognosticators indicating poor overall survival. This study presents the first cross\u2010species transcriptomic analysis of canine HCC, revealing significant molecular resemblances to human HCC, indicating it may be a promising comparative model for studying tumor biology, drug responses, and novel therapeutic interventions.<\/jats:p>","DOI":"10.1002\/mc.70092","type":"journal-article","created":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T10:07:17Z","timestamp":1770718037000},"page":"523-536","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Molecular Insights Into Canine Hepatocellular Carcinoma: A Cross\u2010Species Transcriptomic Comparison With Human HCC"],"prefix":"10.1002","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3432-7696","authenticated-orcid":false,"given":"Mohammad","family":"Arif","sequence":"first","affiliation":[{"name":"Joint Graduate School of Veterinary Medicine Kagoshima University Kagoshima Japan"},{"name":"Department of Microbiology and Hygiene Bangladesh Agricultural University Mymensingh Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8666-972X","authenticated-orcid":false,"given":"MD Nazmul","family":"Hasan","sequence":"additional","affiliation":[{"name":"Joint Graduate School of Veterinary Medicine Kagoshima University Kagoshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7261-3193","authenticated-orcid":false,"given":"Nobuhiro","family":"Nozaki","sequence":"additional","affiliation":[{"name":"Joint Graduate School of Veterinary Medicine Kagoshima University Kagoshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4256-1407","authenticated-orcid":false,"given":"Yutaro","family":"Ide","sequence":"additional","affiliation":[{"name":"Joint Graduate School of Veterinary Medicine Kagoshima University Kagoshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2048-2508","authenticated-orcid":false,"given":"Yoshiyuki","family":"Akiyama","sequence":"additional","affiliation":[{"name":"Joint Graduate School of Veterinary Medicine Kagoshima University Kagoshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7808-777X","authenticated-orcid":false,"given":"Shaohsu","family":"Wang","sequence":"additional","affiliation":[{"name":"Joint Graduate School of Veterinary Medicine Kagoshima University Kagoshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0358-756X","authenticated-orcid":false,"given":"Most Shumi Akhter","family":"Shathi","sequence":"additional","affiliation":[{"name":"Joint Graduate School of Veterinary Medicine Kagoshima University Kagoshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4430-5645","authenticated-orcid":false,"given":"Osamu","family":"Yamato","sequence":"additional","affiliation":[{"name":"Joint Graduate School of Veterinary Medicine Kagoshima University Kagoshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4625-5231","authenticated-orcid":false,"given":"Naoki","family":"Miura","sequence":"additional","affiliation":[{"name":"Joint Graduate School of Veterinary Medicine Kagoshima University Kagoshima Japan"},{"name":"Veterinary Teaching Hospital, Joint Faculty of Veterinary Medicine Kagoshima University Kagoshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,10]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/030098588101800402"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1177\/030098588001700504"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/vetsci9090489"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tvjl.2019.04.011"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.30246"},{"key":"e_1_2_12_7_1","first-page":"811","article-title":"Comparative Analysis of Hepatocellular Carcinoma in Men and Dogs","volume":"33","author":"Grabarevi\u0107 Z.","year":"2009","journal-title":"Collegium Antropologicum"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-023-00977-3"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1086432"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trsl.2011.11.005"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13353-022-00721-z"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-020-0297-3"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetimm.2006.03.006"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1080\/14737140.2022.2074404"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-025-00841-8"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17458-0"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26115152"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines11041100"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2011.07.007"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s44356-025-00037-0"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12051272"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0708857"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2022.05.522"},{"key":"e_1_2_12_24_1","first-page":"16","article-title":"Transcriptome Analysis of Dog Oral Melanoma and Its Oncogenic Analogy With Human Melanoma","volume":"43","author":"Rahman M. M.","year":"2020","journal-title":"Oncology Reports"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/vetsci11080361"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-021-01908-0"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-023-01355-5"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13104-024-07016-y"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2022.146735"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.22441"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1009450"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/vco.12379"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2020.00814"},{"key":"e_1_2_12_34_1","first-page":"133","article-title":"Identification of Potential Hub Genes Related to the Progression and Prognosis of Hepatocellular Carcinoma Through Integrated Bioinformatics Analysis","volume":"43","author":"Song X.","year":"2020","journal-title":"Oncology Reports"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt1248"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.29131"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2017.5890"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1042\/BSR20202564"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5829.2012.00348.x"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI124918"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-021-02967-8"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2008.05.025"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2023.1200114"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13577-020-00362-6"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14010238"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24065212"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1340634"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.2147\/JHC.S336858"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hbpd.2021.09.006"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.109.001289"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/8816070"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1002\/mc.23723"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2023.101170"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3252"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.2147\/JHC.S156701"},{"key":"e_1_2_12_56_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.748269"},{"key":"e_1_2_12_57_1","doi-asserted-by":"publisher","DOI":"10.1097\/HEP.0000000000000005"},{"key":"e_1_2_12_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-023-01028-7"},{"key":"e_1_2_12_59_1","first-page":"47","volume-title":"Nutrient modulation of the immune response","author":"Barbul A.","year":"1992"},{"key":"e_1_2_12_60_1","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/4709300"},{"key":"e_1_2_12_61_1","doi-asserted-by":"publisher","DOI":"10.1155\/2008\/134059"},{"key":"e_1_2_12_62_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.14090"}],"container-title":["Molecular Carcinogenesis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mc.70092","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mc.70092","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mc.70092","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T09:09:25Z","timestamp":1773133765000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mc.70092"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,10]]},"references-count":61,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1002\/mc.70092"],"URL":"https:\/\/doi.org\/10.1002\/mc.70092","archive":["Portico"],"relation":{},"ISSN":["0899-1987","1098-2744"],"issn-type":[{"value":"0899-1987","type":"print"},{"value":"1098-2744","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,10]]},"assertion":[{"value":"2025-10-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}