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, Martin-Garcia, Ana, Mendiburu-Eliçabe, Marina, Prieto, Carlos, Ruiz-Pinto, Sara, Pita, Guillermo, Velasco-Ruiz, Alejandro, Patino-Alonso, María Carmen, Galindo-Villardón, Purificación, Linarejos Vera-Pedrosa, María, Jalife, José, Mao, Jian-Hua, Macías de Plasencia, Guillermo, Castellanos-Martín, Andrés, Sáez-Freire, María Del Mar, Fraile, Susana, Rodrigues Teixeira, Telmo, García-Macías, Carmen, Galvis-Jiménez, Julie Milena, García Sánchez, Asunción, Isidoro-García, María, Fuentes, Manuel, García-Cenador, Begoña, García-Criado, Francisco Javier, García, Juan L., Hernández-García, María Ángeles, Cruz, 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, M., González-Neira, Anna, Sánchez, Pedro L, Pérez-Losada, J. |
| المساهمون: | Ministerio de Ciencia e Innovación (España), Agencia Estatal de Investigación (España), European Commission, Junta de Castilla y León, Instituto de Salud Carlos III, Department of Defense (US), National Institutes of Health (US), National Cancer Institute (US), Lawrence Berkeley National Laboratory, Fundación la Caixa, Centro Nacional de Investigaciones Cardiovasculares (España) |
| بيانات النشر: | Multidisciplinary Digital Publishing Institute |
| سنة النشر: | 2023 |
| المجموعة: | Digital.CSIC (Consejo Superior de Investigaciones Científicas / Spanish National Research Council) |
| مصطلحات موضوعية: | Quantitative trait loci, Anthracyclines, Cardiotoxicity, Complex genetic disease, Intermediate molecular phenotypes |
| الوصف: | This article belongs to the Collection Cardiovascular Disease: From Molecular and Cellular Mechanisms to Therapeutic Opportunities. ; 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 ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2073-4409 |
| العلاقة: | #PLACEHOLDER_PARENT_METADATA_VALUE#; info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-118527RB-I00/ES/EVALUACION DE LA PREVENCION DEL CANCER DE MAMA MEDIANTE ANALOGOS DE LA SOMATOSTATINA/; info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PDC2021-121735-I00/ES/BREAST CANCER PREVENTION BY ENHANCING POSTLACTATIONAL INVOLUTION WITH CABERGOLINE/; Publisher's version; Gómez-Vecino, Aurora; Corchado Cobos, Roberto; Blanco-Gómez, Adrián; Castillo, Sonia; García-Sancha, Natalia; Martin-Garcia, Ana; Prieto, Carlos; Ruiz-Pinto, Sara; Pita, Guillermo; Velasco-Ruiz, Alejandro; Patino-Alonso, María Carmen; Galindo-Villardón, Purificación; Linarejos Vera-Pedrosa, María; Jalife, José; Macías de Plasencia, Guillermo; Castellanos-Martín, Andrés; Sáez-Freire, María del Mar; Mendiburu-Eliçabe, Marina; Fraile, Susana; Rodrigues Teixeira, Telmo; García-Macías, Carmen; Galvis-Jiménez, Julie Milena; García-Sánchez, Asunción; Isidoro-García, María; Fuentes, Manuel; García-Cenador, Begoña; García-Criado, Francisco Javier; García, Juan L.; Hernández-García, María Ángeles; Cruz, Juan Jesús; Rodríguez-Sánchez, César Augusto; Martín-Ruiz, Alejandro; Pérez-López, Estefanía; Pérez-Martínez, Antonio; Gutiérrez-Larraya, Federico; Cartón, Antonio J.; García-Saenz, José Ángel; Patiño-García, Ana; Martin, Miguel; Alonso Gordoa, Teresa; Vulsteke, Christof; Croes, Lieselot; Hatse, Sigrid; Van Brussel, Thomas; Lambrechts, Diether; Wildiers, Hans; Holgado-Madruga, M.; González-Neira, Ana; Sánchez, Pedro L.; Pérez-Losada, J.; 2021; Datasets related to a study aimed to identify genetic markers of CDA by subphenotypes associated with cardiotoxicity; DIGITAL.CSIC; http://dx.doi.org/10.20350/digitalCSIC/13845Test; https://doi.org/10.3390/cells12151956Test; Sí; Cells 12(15): 1956 (2023); http://hdl.handle.net/10261/345361Test; http://dx.doi.org/10.13039/100000002Test; http://dx.doi.org/10.13039/501100014180Test; http://dx.doi.org/10.13039/100006235Test; http://dx.doi.org/10.13039/501100004837Test; http://dx.doi.org/10.13039/501100011033Test; http://dx.doi.org/10.13039/501100005884Test; http://dx.doi.org/10.13039/100000005Test; http://dx.doi.org/10.13039/501100000780Test; http://dx.doi.org/10.13039/501100004587Test; 2-s2.0-85167704764; https://api.elsevier.com/content/abstract/scopus_id/85167704764Test |
| DOI: | 10.3390/cells12151956 |
| DOI: | 10.13039/100000002 |
| DOI: | 10.13039/501100014180 |
| DOI: | 10.13039/100006235 |
| DOI: | 10.13039/501100004837 |
| DOI: | 10.13039/501100011033 |
| DOI: | 10.13039/501100005884 |
| DOI: | 10.13039/100000005 |
| DOI: | 10.13039/501100000780 |
| DOI: | 10.13039/501100004587 |
| الإتاحة: | https://doi.org/10.3390/cells1215195610.13039/10000000210.13039/50110001418010.13039/10000623510.13039/50110000483710.13039/50110001103310.13039/50110000588410.13039/10000000510.13039/50110000078010.13039/50110000458710.20350/digitalCSIC/13845Test http://hdl.handle.net/10261/345361Test https://api.elsevier.com/content/abstract/scopus_id/85167704764Test |
| حقوق: | open |
| رقم الانضمام: | edsbas.B4A9B1CB |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 20734409 |
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| DOI: | 10.3390/cells12151956 |