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 |
|---|---|
| المؤلفون: | Gomez-Vecino, Aurora, Corchado-Cobos, Roberto, Blanco-Gomez, Adrian, Garcia-Sancha, Natalia, Castillo-Lluva, Sonia, Martin-Garcia, Ana, Mendiburu-Elicabe, Marina, Prieto, Carlos, Ruiz-Pinto, Sara, Pita, Guillermo, Velasco-Ruiz, Alejandro, Patino-Alonso, Carmen, Galindo-Villardon, Purificacion, Vera-Pedrosa, Maria Linarejos, Jalife, Jose, Mao, Jian-Hua, de Plasencia, Guillermo Macias, Castellanos-Martin, Andres, Saez-Freire, Maria del Mar, Fraile-Martin, Susana, Rodrigues-Teixeira, Telmo, Garcia-Macias, Carmen, Galvis-Jimenez, Julie Milena, Garcia-Sanchez, Asuncion, Isidoro-Garcia, Maria, Fuentes, Manuel, Garcia-Cenador, Maria Begona, Garcia-Criado, Francisco Javier, Garcia-Hernandez, Juan Luis, Hernandez-Garcia, Maria Angeles, Cruz-Hernandez, Juan Jesus, Rodriguez-Sanchez, Cesar Augusto, Garcia-Sancho, Alejandro Martin, Perez-Lopez, Estefania, Perez-Martinez, Antonio, Gutierrez-Larraya, Federico, Carton, Antonio J., Garcia-Saenz, Jose Angel, Patino-Garcia, Ana, Martin, Miguel, Alonso-Gordoa, Teresa, Vulsteke, Christof, Croes, Lieselot, Hatse, Sigrid, Van Brussel, Thomas, Lambrechts, Diether, Wildiers, Hans, Chang, Hang, Holgado-Madruga, Marina, Gonzalez-Neira, Anna, Sanchez, Pedro L., Losada, Jesu Perez |
| المصدر: | 2073-4409 ; Cells |
| سنة النشر: | 2023 |
| المجموعة: | IRUA - Institutional Repository van de Universiteit Antwerpen |
| مصطلحات موضوعية: | Biology, Human medicine |
| 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/isi/001045566200001 |
| الإتاحة: | https://doi.org/10.3390/CELLS12151956Test https://hdl.handle.net/10067/1984690151162165141Test https://repository.uantwerpen.be/docstore/d:irua:19068Test |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.7358CFDD |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |