دورية أكاديمية
Intermediate Molecular Phenotypes to Identify Genetic Markers of Anthracycline-Induced Cardiotoxicity Risk.
| العنوان: | Intermediate Molecular Phenotypes to Identify Genetic Markers of Anthracycline-Induced Cardiotoxicity Risk. |
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| المؤلفون: | Gómez-Vecino, Aurora, Corchado-Cobos, Roberto, Blanco-Gómez, Adrián, García-Sancha, Natalia, Castillo-Lluva, Sonia, Martín-García, Ana, Mendiburu-Eliçabe, Marina, Prieto, Carlos, Ruiz-Pinto, Sara, Pita, Guillermo, Velasco-Ruiz, Alejandro, Patino-Alonso, Carmen, Galindo-Villardón, Purificación, Vera-Pedrosa, María Linarejos, Jalife, Jose, Mao, Jian-Hua, Macías de Plasencia, Guillermo, Castellanos-Martín, Andrés, Sáez-Freire, María Del Mar, Fraile-Martín, Susana, Rodrigues-Teixeira, Telmo, García-Macías, Carmen, Galvis-Jiménez, Julie Milena, García-Sánchez, Asunción, Isidoro-García, María, Fuentes, Manuel, García-Cenador, María Begoña, García-Criado, Francisco Javier, García-Hernández, Juan Luis, Hernández-García, María Ángeles, Cruz-Hernández, Juan Jesús, Rodríguez-Sánchez, César Augusto, García-Sancho, Alejandro Martín, Pérez-López, Estefanía, Pérez-Martínez, Antonio, Gutiérrez-Larraya, Federico, Cartón, Antonio J, García-Sáenz, José Ángel, Patiño-García, Ana, Martín, Miguel, Alonso-Gordoa, Teresa, Vulsteke, Christof, Croes, Lieselot, Hatse, Sigrid, Van Brussel, Thomas, Lambrechts, Diether, Wildiers, Hans, Chang, Hang, Holgado-Madruga, Marina, González-Neira, Anna, Sánchez, Pedro L, Pérez Losada, Jesús |
| المساهمون: | Instituto de Salud Carlos III, Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF), Ministerio de Ciencia y Competitividad (España), Ministerio de Ciencia e Innovación. Centro de Excelencia Severo Ochoa (España), Fundación La Caixa |
| بيانات النشر: | Multidisciplinary Digital Publishing Institute (MDPI) |
| سنة النشر: | 2023 |
| المجموعة: | REPISALUD (REPositorio Institucional en SALUD del Instituto de Salud Carlos III - ISCIII) |
| مصطلحات موضوعية: | Cardiotoxicity, Neoplasms, Female, Animals, Mice, Anthracyclines, Genetic Markers, Antibiotics, Antineoplastic, Phenotype |
| الوصف: | Cardiotoxicity due to anthracyclines (CDA) affects cancer patients, but we cannot predict who may suffer from this complication. CDA is a complex trait with a polygenic component that is mainly unidentified. We propose that levels of intermediate molecular phenotypes (IMPs) in the myocardium associated with histopathological damage could explain CDA susceptibility, so variants of genes encoding these IMPs could identify patients susceptible to this complication. Thus, a genetically heterogeneous cohort of mice (n = 165) generated by backcrossing were treated with doxorubicin and docetaxel. We quantified heart fibrosis using an Ariol slide scanner and intramyocardial levels of IMPs using multiplex bead arrays and QPCR. We identified quantitative trait loci linked to IMPs (ipQTLs) and cdaQTLs via linkage analysis. In three cancer patient cohorts, CDA was quantified using echocardiography or Cardiac Magnetic Resonance. CDA behaves as a complex trait in the mouse cohort. IMP levels in the myocardium were associated with CDA. ipQTLs integrated into genetic models with cdaQTLs account for more CDA phenotypic variation than that explained by cda-QTLs alone. Allelic forms of genes encoding IMPs associated with CDA in mice, including AKT1, MAPK14, MAPK8, STAT3, CAS3, and TP53, are genetic determinants of CDA in patients. Two genetic risk scores for pediatric patients (n = 71) and women with breast cancer (n = 420) were generated using machine-learning Least Absolute Shrinkage and Selection Operator (LASSO) regression. Thus, IMPs associated with heart damage identify genetic markers of CDA risk, thereby allowing more personalized patient management. ; J.P.L.’s lab is sponsored by Grant PID2020-118527RB-I00 funded by MCIN/AEI/10.13039/ 501100011039; Grant PDC2021-121735-I00 funded by MCIN/AEI/10.13039/501100011039 and by the “European Union Next Generation EU/PRTR”, the Regional Government of Castile and León (CSI144P20). J.P.L. and P.L.S. are supported by the Carlos III Health Institute (PIE14/00066). AGN laboratory and ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 2073-4409 |
| العلاقة: | info:eu-repo/grantAgreement/ES/PID2020-118527RB-I00; info:eu-repo/grantAgreement/ES/MCIN/AEI/10.13039/501100011039; info:eu-repo/grantAgreement/ES/PDC2021-121735-I00; info:eu-repo/grantAgreement/ES/PIE14/00066; info:eu-repo/grantAgreement/ES/PI18/01242; info:eu-repo/grantAgreement/ES/PT17/0019; info:eu-repo/grantAgreement/ES/RTI2018-094130-B-100; info:eu-repo/grantAgreement/ES/HR18-00304; info:eu-repo/grantAgreement/ES/12-2016/IGP; Cells. 2023 Jul 27;12(15):1956.; http://hdl.handle.net/20.500.12105/16571Test; Cells |
| DOI: | 10.3390/cells12151956 |
| الإتاحة: | https://doi.org/20.500.12105/16571Test https://doi.org/10.3390/cells12151956Test https://hdl.handle.net/20.500.12105/16571Test |
| حقوق: | http://creativecommons.org/licenses/by/4.0Test/ ; Atribución 4.0 Internacional ; open access |
| رقم الانضمام: | edsbas.1EC1F48F |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 20734409 |
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| DOI: | 10.3390/cells12151956 |