Metabolomic Analysis Points to Bioactive Lipid Species and Acireductone Dioxygenase 1 (ADI1) as Potential Therapeutic Targets in Poor Prognosis Endometrial Cancer

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dc.contributor.authorGatius Calderó, Sònia
dc.contributor.authorJové Font, Mariona
dc.contributor.authorMegino-Luque, Cristina
dc.contributor.authorAlbertí Valls, Manel
dc.contributor.authorYeramian Hakim, Andree
dc.contributor.authorBonifaci, Núria
dc.contributor.authorPinyol, Miquel
dc.contributor.authorSantacana Espasa, Maria
dc.contributor.authorPradas Barriga, Irene
dc.contributor.authorLlobet Navàs, David
dc.contributor.authorPamplona Gras, Reinald
dc.contributor.authorMatias-Guiu, Xavier
dc.contributor.authorEritja Sánchez, Núria
dc.date.accessioned2022-12-08T16:53:04Z
dc.date.available2022-12-08T16:53:04Z
dc.date.issued2022
dc.description.abstractMetabolomic profiling analysis has the potential to highlight new molecules and cellular pathways that may serve as potential therapeutic targets for disease treatment. In this study, we used an LC-MS/MS platform to define, for the first time, the specific metabolomic signature of uterine serous carcinoma (SC), a relatively rare and aggressive variant of endometrial cancer (EC) responsible for 40% of all endometrial cancer-related deaths. A metabolomic analysis of 31 ECs (20 endometrial endometrioid carcinomas (EECs) and 11 SCs) was performed. Following multivariate statistical analysis, we identified 232 statistically different metabolites among the SC and EEC patient samples. Notably, most of the metabolites identified (89.2%) were lipid species and showed lower levels in SCs when compared to EECs. In addition to lipids, we also documented metabolites belonging to amino acids and purine nucleotides (such as 2-Oxo-4-methylthiobutanoic acid, synthesised by acireductone dioxygenase 1 (ADI1) enzyme), which showed higher levels in SCs. To further investigate the role of ADI1 in SC, we analysed the expression protein levels of ADI1 in 96 ECs (67 EECs and 29 SCs), proving that the levels of ADI1 were higher in SCs compared to EECs. We also found that ADI1 mRNA levels were higher in p53 abnormal ECs compared to p53 wild type tumours. Furthermore, elevated ADI1 mRNA levels showed a statistically significant negative correlation with overall survival and progression-free survival among EEC patients. Finally, we tested the ability of ADI1 to induce migration and invasion capabilities in EC cell lines. Altogether, these results suggest that ADI1 could be a potential therapeutic target in poor-prognosis SCs and other Ecs with abnormal p53 expression.ca_ES
dc.description.sponsorshipThis study was funded by the Instituto de Salud Carlos III (ISCIII) through projects PI20/00502, CP19/00025, CB16/12/00231, PI16/00692, PI18/00573, PI21/00672, CP17/00063 and PI18/00795; and by the Spanish Ministry of Science, Innovation and Universities (Ministerio de Ciencia, Innovación y Universidades, RTI2018-099200-BI00), co-funded by the European Regional Development Fund (ERDF) as part of the “A way to make Europe” programme and the European Social Fund (ESF) as part of the “Investing in Your Future” programme. This study was also supported by the “Xarxa de Bancs de Tumors de Catalunya” and sponsored by “Pla Director d’Oncologia de Catalunya (XBTC)”, “IRBLleida Biobank” (B.0000682) and “Plataforma Biobancos” PT20/00021. We also thank the Generalitat of Catalonia: Agency for Management of University and Research Grants (2017SGR1368 and 2017SGR696) and the “Asociación Española Contra el Cáncer” (AECC; Grupos Estables 2018 and LABAE19004LLOB). M.J. is a Serra Húnter Fellow. N.E. (MS19/00025) and D.L-N. (MS17/00063) are recipients of a Miguel Servet research scheme (co-funded by the ESF program “Investing in Your Future”). C. M-L. holds a predoctoral fellowship from the Generalitat de Catalunya (2020FI_B2 00099) and the predoctoral fellowship “Ajuts 2021 de Promoció de la Recerca en Salut-9a edició” from IRBLleida/Diputació de Lleida. IRBLleida is a CERCA Program/Generalitat of Catalonia.ca_ES
dc.identifier.doihttps://doi.org/10.3390/cancers14122842
dc.identifier.idgrec032655
dc.identifier.issn2072-6694
dc.identifier.urihttp://hdl.handle.net/10459.1/84493
dc.language.isoengca_ES
dc.publisherMDPIca_ES
dc.relationinfo:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)/PI20%2F00502/ES/PAPEL DE ARID1A EN LA CARCINOGENESIS ENDOMETRIAL DEPENDIENTE DE CONTEXTO. ANALISIS DE LOS MECANISMOS MOLECULARES Y POSIBLES IMPLICACIONES TERAPEUTICAS/ca_ES
dc.relationinfo:eu-repo/grantAgreement/MINECO//CB16%2F12%2F00231/ES/CANCER/ca_ES
dc.relationinfo:eu-repo/grantAgreement/MINECO//PI16%2F00692/ES/Perfiles epigenéticos asociados a patrones de metástasis en cáncer de endometrio/ca_ES
dc.relationinfo:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016 (ISCIII)/PI18%2F00573/ES/ANALISIS DEL SECRETOMA EN EL MELANOMA HUMANO ASOCIADO AL PERFIL GENETICO Y A LA APARICION DE RESISTENCIAS. IDENTIFICACION DE BIOMARCADORES Y%2FO DIANAS TERAPEUTICAS DE APLICACION CLINICA/ca_ES
dc.relationinfo:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)/PI21%2F00672/ES/UNDERSTANDING MECHANISMS OF ANTI-ANGIOGENIC THERAPY RESISTANCE AND PROGRESSION IN ENDOMETRIAL CANCER./ca_ES
dc.relationinfo:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016 (ISCIII)/PI18%2F00795/ES/IDENTIFICACION DE LOS MECANISMOS QUE CONDUCEN A LA RESISTENCIA A ANOIKIS Y LA DISEMINACION METASTASICA EN TUMORES GINECOLOGICOS CON ALTO CONTENIDO EN SCNA/ca_ES
dc.relationinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-099200-B-I00/ES/NEUROLIPIDOMICA DEL ENVEJECIMIENTO CEREBRAL HUMANO/ca_ES
dc.relation.isformatofReproducció del document publicat a https://doi.org/10.3390/cancers14122842ca_ES
dc.relation.ispartofCancers, 2022, vol. 14, núm. 12, art. 2842.ca_ES
dc.rightscc-by (c) Sònia Gatius Calderó et al., 2022ca_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccessca_ES
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectSerous endometrial cancerca_ES
dc.subjectMetabolomics profileca_ES
dc.subjectBioactive lipid speciesca_ES
dc.subjectADI1ca_ES
dc.subjectEndometrial cancerca_ES
dc.titleMetabolomic Analysis Points to Bioactive Lipid Species and Acireductone Dioxygenase 1 (ADI1) as Potential Therapeutic Targets in Poor Prognosis Endometrial Cancerca_ES
dc.typeinfo:eu-repo/semantics/articleca_ES
dc.type.versioninfo:eu-repo/semantics/publishedVersionca_ES
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