{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T19:13:28Z","timestamp":1785266008130,"version":"3.55.0"},"reference-count":52,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,2,21]],"date-time":"2023-02-21T00:00:00Z","timestamp":1676937600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Princess Margaret Cancer Research Foundation"},{"name":"University Health Network, Toronto, Canada"},{"name":"Canadian Mesothelioma Research Foundation, Canada"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Malignant mesothelioma (MESO) consists of epithelioid, biphasic, and sarcomatoid subtypes with different epithelial\u2013mesenchymal transition (EMT) phenotypes. We previously identified a panel of four MESO EMT genes correlating with an immunosuppressive tumor microenvironment and poor survival. In this study, we investigated the correlation between these MESO EMT genes, the immune profile, and the genomic and epigenomic alterations to identify potential therapeutic targets to prevent or reverse the EMT process. Using multiomic analysis, we observed that the MESO EMT genes were positively correlated with hypermethylation of epigenetic genes and loss of CDKN2A\/B expression. MESO EMT genes such as COL5A2, ITGAV, SERPINH1, CALD1, SPARC, and ACTA2 were associated with upregulation of TGF-\u03b2 signaling, hedgehog signaling, and IL-2-STAT5 signaling and downregulation of the IFN-\u03b1 and IFN-\u03b3 response. Immune checkpoints such as CTLA4, CD274 (PD-L1), PDCD1LG2 (PD-L2), PDCD1 (PD-1), and TIGIT were upregulated, while LAG3, LGALS9, and VTCN1 were downregulated with the expression of MESO EMT genes. CD160, KIR2DL1, and KIR2DL3 were also broadly downregulated with the expression of MESO EMT genes. In conclusion, we observed that the expression of a panel of MESO EMT genes was associated with hypermethylation of epigenetic genes and loss of expression of CDKN2A and CDKN2B. Expression of MESO EMT genes was associated with downregulation of the type I and type II IFN response, loss of cytotoxicity and NK cell activity, and upregulation of specific immune checkpoints, as well as upregulation of the TGF-\u03b21\/TGFBR1 pathway.<\/jats:p>","DOI":"10.3390\/ijms24054264","type":"journal-article","created":{"date-parts":[[2023,2,21]],"date-time":"2023-02-21T03:04:12Z","timestamp":1676948652000},"page":"4264","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Prognostic Value of EMT Gene Signature in Malignant Mesothelioma"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4803-9361","authenticated-orcid":false,"given":"Licun","family":"Wu","sequence":"first","affiliation":[{"name":"Latner Thoracic Surgery Research Laboratories, Division of Thoracic Surgery, Toronto General Hospital, Princess Margaret Cancer Research Centre, University Health Network, University of Toronto, Toronto, ON M5G 1L7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2254-3378","authenticated-orcid":false,"given":"Kosuke","family":"Yoshihara","sequence":"additional","affiliation":[{"name":"Institute for Research Promotion, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8510, Japan"},{"name":"Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hana","family":"Yun","sequence":"additional","affiliation":[{"name":"Latner Thoracic Surgery Research Laboratories, Division of Thoracic Surgery, Toronto General Hospital, Princess Margaret Cancer Research Centre, University Health Network, University of Toronto, Toronto, ON M5G 1L7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saraf","family":"Karim","sequence":"additional","affiliation":[{"name":"Latner Thoracic Surgery Research Laboratories, Division of Thoracic Surgery, Toronto General Hospital, Princess Margaret Cancer Research Centre, University Health Network, University of Toronto, Toronto, ON M5G 1L7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nastaran","family":"Shokri","sequence":"additional","affiliation":[{"name":"Latner Thoracic Surgery Research Laboratories, Division of Thoracic Surgery, Toronto General Hospital, Princess Margaret Cancer Research Centre, University Health Network, University of Toronto, Toronto, ON M5G 1L7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatemeh","family":"Zaeimi","sequence":"additional","affiliation":[{"name":"Latner Thoracic Surgery Research Laboratories, Division of Thoracic Surgery, Toronto General Hospital, Princess Margaret Cancer Research Centre, University Health Network, University of Toronto, Toronto, ON M5G 1L7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. S. Jeffrey","family":"Man","sequence":"additional","affiliation":[{"name":"Latner Thoracic Surgery Research Laboratories, Division of Thoracic Surgery, Toronto General Hospital, Princess Margaret Cancer Research Centre, University Health Network, University of Toronto, Toronto, ON M5G 1L7, Canada"},{"name":"Department of Immunology, University of Toronto, Toronto, ON M5S 2E8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amin","family":"Zia","sequence":"additional","affiliation":[{"name":"Latner Thoracic Surgery Research Laboratories, Division of Thoracic Surgery, Toronto General Hospital, Princess Margaret Cancer Research Centre, University Health Network, University of Toronto, Toronto, ON M5G 1L7, Canada"},{"name":"Dycode Bio, Co., Toronto, ON L6C 2R9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3408-0294","authenticated-orcid":false,"given":"Emanuela","family":"Felley-Bosco","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Oncology, Department of Thoracic Surgery, University Hospital Zurich, 8091 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2000-9427","authenticated-orcid":false,"given":"Marc","family":"de Perrot","sequence":"additional","affiliation":[{"name":"Latner Thoracic Surgery Research Laboratories, Division of Thoracic Surgery, Toronto General Hospital, Princess Margaret Cancer Research Centre, University Health Network, University of Toronto, Toronto, ON M5G 1L7, Canada"},{"name":"Department of Immunology, University of Toronto, Toronto, ON M5S 2E8, Canada"},{"name":"Institute of Medical Science, University of Toronto, Toronto, ON M5G 2C4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.1056\/NEJM198906293202604","article-title":"Asbestos-Related Diseases","volume":"320","author":"Mossman","year":"1989","journal-title":"New Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"693814","DOI":"10.3389\/fonc.2021.693814","article-title":"Carbon Nanotubes: A Summary of Beneficial and Dangerous Aspects of an Increasingly Popular Group of Nanomaterials","volume":"11","author":"Zhang","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1001\/jamaoncol.2019.0446","article-title":"High Time for Complete Ban on Asbestos Use in Developing Countries","volume":"5","author":"Chen","year":"2019","journal-title":"JAMA Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/S1470-2045(20)30606-9","article-title":"Surgery for malignant pleural mesothelioma after radiotherapy (SMART): Final results from a single-centre, phase 2 trial","volume":"22","author":"Cho","year":"2021","journal-title":"Lancet Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"eabd9882","DOI":"10.1126\/scitranslmed.abd9882","article-title":"Triple-modality therapy maximizes antitumor immune responses in a mouse model of mesothelioma","volume":"13","author":"Murakami","year":"2021","journal-title":"Sci. Transl. Med."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Aoki, M., Wu, L., Murakami, J., Zhao, Y., Yun, H., and de Perrot, M. (2021). IRF3 Knockout Results in Partial or Complete Rejection of Murine Mesothelioma. J. Clin. Med., 10.","DOI":"10.3390\/jcm10215196"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/S0140-6736(20)32714-8","article-title":"First-line nivolumab plus ipilimumab in unresectable malignant pleural mesothelioma (CheckMate 743): A multicentre, randomised, open-label, phase 3 trial","volume":"397","author":"Baas","year":"2021","journal-title":"Lancet"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1200\/OP.21.00426","article-title":"Management of Advanced Pleural Mesothelioma\u2014At the Crossroads","volume":"18","author":"Nowak","year":"2022","journal-title":"JCO Oncol. Prac."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"924","DOI":"10.21037\/tlcr.2020.03.38","article-title":"Clinical significance of histologic subtyping of malignant pleural mesothelioma","volume":"9","author":"Brcic","year":"2020","journal-title":"Transl. Lung Cancer Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1038\/nrc.2017.118","article-title":"EMT in cancer","volume":"18","author":"Brabletz","year":"2018","journal-title":"Nat. Rev. Cancer"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"5962","DOI":"10.1158\/1078-0432.CCR-20-2077","article-title":"Epithelial-to-Mesenchymal Transition is a Cause of Both Intrinsic and Acquired Resistance to KRAS G12C Inhibitor in KRAS G12C\u2013Mutant Non\u2013Small Cell Lung Cancer","volume":"26","author":"Adachi","year":"2020","journal-title":"Clin. Cancer Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"103798","DOI":"10.1016\/j.isci.2022.103798","article-title":"Machine learning for multi-omics data integration in cancer","volume":"25","author":"Cai","year":"2022","journal-title":"Iscience"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-022-27953-1","article-title":"Tissue-specific multi-omics analysis of atrial fibrillation","volume":"13","author":"Assum","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"104056","DOI":"10.1016\/j.isci.2022.104056","article-title":"Multi-omics & pathway analysis identify potential roles for tumor N-acetyl aspartate accumulation in murine models of castration-resistant prostate cancer","volume":"25","author":"Salji","year":"2022","journal-title":"Iscience"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1038\/s41416-020-01178-9","article-title":"EMTome: A resource for pan-cancer analysis of epithelial-mesenchymal transition genes and signatures","volume":"124","author":"Vasaikar","year":"2020","journal-title":"Br. J. Cancer"},{"key":"ref_16","first-page":"1","article-title":"A panel of emerging EMT genes identified in malignant mesothelioma","volume":"12","author":"Wu","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"699385","DOI":"10.3389\/fgene.2021.699385","article-title":"Analysis of Immune\u2013Stromal Score-Based Gene Signature and Molecular Subtypes in Osteosarcoma: Implications for Prognosis and Tumor Immune Microenvironment","volume":"12","author":"Zheng","year":"2021","journal-title":"Front. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1158\/1078-0432.CCR-15-0876","article-title":"A Patient-Derived, Pan-Cancer EMT Signature Identifies Global Molecular Alterations and Immune Target Enrichment Following Epithelial-to-Mesenchymal Transition","volume":"22","author":"Mak","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1038\/s41416-021-01462-2","article-title":"Biological basis for novel mesothelioma therapies","volume":"125","author":"Obacz","year":"2021","journal-title":"Br. J. Cancer"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1038\/modpathol.2011.144","article-title":"Epithelial\u2013mesenchymal transition in malignant mesothelioma","volume":"25","author":"Fassina","year":"2012","journal-title":"Mod. Pathol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1158\/1541-7786.MCR-21-0230","article-title":"A Novel Therapeutic Strategy Targeting the Mesenchymal Phenotype of Malignant Pleural Mesothelioma by Suppressing LSD1","volume":"20","author":"Wirawan","year":"2022","journal-title":"Mol. Cancer Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1038\/s41586-019-1897-5","article-title":"TGF-\u03b2 orchestrates fibrogenic and developmental EMTs via the RAS effector RREB1","volume":"577","author":"Su","year":"2020","journal-title":"Nature"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e2102050118","DOI":"10.1073\/pnas.2102050118","article-title":"Identification of EMT signaling cross-talk and gene regulatory networks by single-cell RNA sequencing","volume":"118","author":"Deshmukh","year":"2021","journal-title":"Proc. Natl. Acad. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"793881","DOI":"10.3389\/fonc.2021.793881","article-title":"Pan-Cancer Analysis Shows Enrichment of Macrophages, Overexpression of Checkpoint Molecules, Inhibitory Cytokines, and Immune Exhaustion Signatures in EMT-High Tumors","volume":"11","author":"Tiwari","year":"2022","journal-title":"Front. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.canlet.2013.02.048","article-title":"The relevance of the TGF-\u03b2 Paradox to EMT-MET programs","volume":"341","author":"Morrison","year":"2013","journal-title":"Cancer Lett."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13073-022-01060-8","article-title":"Comprehensive genomic and tumour immune profiling reveals potential therapeutic targets in malignant pleural mesothelioma","volume":"14","author":"Creaney","year":"2022","journal-title":"Genome Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3652","DOI":"10.1038\/s41598-020-60707-x","article-title":"Epithelial-mesenchymal transition gene signature is associated with prognosis and tumor microenvironment in head and neck squamous cell carcinoma","volume":"10","author":"Jung","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Hao, Y., Baker, D., and Dijke, P.T. (2019). TGF-\u03b2-Mediated Epithelial-Mesenchymal Transition and Cancer Metastasis. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20112767"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"697955","DOI":"10.3389\/fonc.2021.697955","article-title":"Differential Impact of TGFB1 Variation by Metastatic Status in Androgen-Deprivation Therapy for Prostate Cancer","volume":"11","author":"Shiota","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e8489","DOI":"10.7717\/peerj.8489","article-title":"EMT-related gene expression is positively correlated with immunity and may be derived from stromal cells in osteosarcoma","volume":"8","author":"Peng","year":"2020","journal-title":"PeerJ"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"6945","DOI":"10.1158\/0008-5472.CAN-10-0785","article-title":"Reciprocal Activation of Prostate Cancer Cells and Cancer-Associated Fibroblasts Stimulates Epithelial-Mesenchymal Transition and Cancer Stemness","volume":"70","author":"Giannoni","year":"2010","journal-title":"Cancer Res."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Czekay, R.-P., Cheon, D.-J., Samarakoon, R., Kutz, S.M., and Higgins, P.J. (2022). Cancer-Associated Fibroblasts: Mechanisms of Tumor Progression and Novel Therapeutic Targets. Cancers, 14.","DOI":"10.3390\/cancers14051231"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-021-91102-9","article-title":"Comprehensive profiling of novel epithelial\u2013mesenchymal transition mediators and their clinical significance in colorectal cancer","volume":"11","author":"Ishikawa","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_34","first-page":"1","article-title":"Cancer-associated fibroblast-derived SDF-1 induces epithelial-mesenchymal transition of lung adenocarcinoma via CXCR4\/\u03b2-catenin\/PPAR\u03b4 signalling","volume":"12","author":"Wang","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1016\/j.trecan.2020.06.005","article-title":"Targeting EMT in Cancer with Repurposed Metabolic Inhibitors","volume":"6","author":"Ramesh","year":"2020","journal-title":"Trends Cancer"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Sage, A.P., Martinez, V.D., Minatel, B.C., Pewarchuk, M.E., Marshall, E.A., MacAulay, G.M., Hubaux, R., Pearson, D.D., Goodarzi, A.A., and Dellaire, G. (2018). Genomics and Epigenetics of Malignant Mesothelioma. High Throughput., 7.","DOI":"10.3390\/ht7030020"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1038\/ng.3520","article-title":"Comprehensive genomic analysis of malignant pleural mesothelioma identifies recurrent mutations, gene fusions and splicing alterations","volume":"48","author":"Bueno","year":"2016","journal-title":"Nat. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1016\/j.jtho.2021.09.012","article-title":"Molecular Characterization of Peritoneal Mesotheliomas","volume":"17","author":"Offin","year":"2022","journal-title":"J. Thorac. Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.lungcan.2021.10.019","article-title":"The highlights of the 15th international conference of the international mesothelioma interest group\u2013Do molecular concepts challenge the traditional approach to pathological mesothelioma diagnosis?","volume":"163","author":"Klebe","year":"2021","journal-title":"Lung Cancer"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"350","DOI":"10.21037\/tlcr.2017.06.06","article-title":"Targeting the epigenome in malignant pleural mesothelioma","volume":"6","author":"McLoughlin","year":"2017","journal-title":"Transl. Lung Cancer Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1172\/JCI36183","article-title":"Biomarkers for epithelial-mesenchymal transitions","volume":"119","author":"Zeisberg","year":"2009","journal-title":"J. Clin. Investig."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"323","DOI":"10.2217\/epi-2022-0008","article-title":"Epigenetics, environment and epidemiology: An interview with Karl Kelsey","volume":"14","author":"Kelsey","year":"2022","journal-title":"Epigenomics"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12967-021-03065-0","article-title":"Comprehensive analysis of EMT-related genes and lncRNAs in the prognosis, immunity, and drug treatment of colorectal cancer","volume":"19","author":"Yang","year":"2021","journal-title":"J. Transl. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1016\/j.drudis.2021.10.020","article-title":"Drug discovery for epigenetics targets","volume":"27","author":"Holdgate","year":"2022","journal-title":"Drug Discov. Today"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1007\/s11626-015-9885-z","article-title":"Establishment of immortalized murine mesothelial cells and a novel mesothelioma cell line","volume":"51","author":"Blum","year":"2015","journal-title":"In Vitro Cell Dev. Biol. Anim."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1016\/j.stemcr.2017.02.005","article-title":"Stem Cell Factor-Based Identification and Functional Properties of In Vitro-Selected Subpopulations of Malignant Mesothelioma Cells","volume":"8","author":"Blum","year":"2017","journal-title":"Stem Cell Rep."},{"key":"ref_47","first-page":"1","article-title":"Epithelial-mesenchymal transition (EMT) signature is inversely associated with T-cell infiltration in non-small cell lung cancer (NSCLC)","volume":"8","author":"Chae","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1056\/NEJMra1912719","article-title":"Perspectives on the Treatment of Malignant Pleural Mesothelioma","volume":"385","author":"Janes","year":"2021","journal-title":"New Engl. J. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1002\/1878-0261.12651","article-title":"Genetic alterations of malignant pleural mesothelioma: Association with tumor heterogeneity and overall survival","volume":"14","author":"Quetel","year":"2020","journal-title":"Mol. Oncol."},{"key":"ref_50","first-page":"1997","article-title":"Genomic landscape of pleural and peritoneal mesothelioma tumors","volume":"127","author":"Hiltbrunner","year":"2022","journal-title":"Lancet"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1751","DOI":"10.1038\/s41467-021-21798-w","article-title":"Clonal architecture in mesothelioma is prognostic and shapes the tumour microenvironment","volume":"12","author":"Zhang","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.it.2019.02.004","article-title":"Targeting DNA Methylation and EZH2 Activity to Overcome Melanoma Resistance to Immunotherapy","volume":"40","author":"Chatterjee","year":"2019","journal-title":"Trends Immunol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/5\/4264\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:37:55Z","timestamp":1760121475000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/5\/4264"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,21]]},"references-count":52,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["ijms24054264"],"URL":"https:\/\/doi.org\/10.3390\/ijms24054264","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,21]]}}}