| Autor: |
Justo-Garrido M; Cancer Research Unit, Institute of Biomedical Research, National Autonomous University of Mexico (UNAM)-National Institute of Cancerology, San Fernando Av #22, XVI Section, Mexico City 14080, Mexico., López-Saavedra A; Cancer Research Unit, Institute of Biomedical Research, National Autonomous University of Mexico (UNAM)-National Institute of Cancerology, San Fernando Av #22, XVI Section, Mexico City 14080, Mexico., Alcaraz N; The Bioinformatics Centre, Department of Biology, University of Copenhagen, 2200 Copenhagen, Denmark.; Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, 1165 Copenhagen, Denmark., Cortés-González CC; Cancer Research Unit, Institute of Biomedical Research, National Autonomous University of Mexico (UNAM)-National Institute of Cancerology, San Fernando Av #22, XVI Section, Mexico City 14080, Mexico., Oñate-Ocaña LF; Department of Gastroenterology, National Cancer Institute (INCan), Tlalpan, Mexico City 14080, Mexico., Caro-Sánchez CHS; Molecular Pathology and Immunology, National Cancer Institute (INCan), Tlalpan, Mexico City 14080, Mexico., Castro-Hernández C; Cancer Research Unit, Institute of Biomedical Research, National Autonomous University of Mexico (UNAM)-National Institute of Cancerology, San Fernando Av #22, XVI Section, Mexico City 14080, Mexico., Arriaga-Canon C; Cancer Research Unit, Institute of Biomedical Research, National Autonomous University of Mexico (UNAM)-National Institute of Cancerology, San Fernando Av #22, XVI Section, Mexico City 14080, Mexico., Díaz-Chávez J; Cancer Research Unit, Institute of Biomedical Research, National Autonomous University of Mexico (UNAM)-National Institute of Cancerology, San Fernando Av #22, XVI Section, Mexico City 14080, Mexico., Herrera LA; Cancer Research Unit, Institute of Biomedical Research, National Autonomous University of Mexico (UNAM)-National Institute of Cancerology, San Fernando Av #22, XVI Section, Mexico City 14080, Mexico.; School of Medicine and Health Sciences-Tecnológico de Monterrey, Mexico City 14380, Mexico. |
| Abstrakt: |
Chemoresistance to standard neoadjuvant treatment commonly occurs in locally advanced breast cancer, particularly in the luminal subtype, which is hormone receptor-positive and represents the most common subtype of breast cancer associated with the worst outcomes. Identifying the genes associated with chemoresistance is crucial for understanding the underlying mechanisms and discovering effective treatments. In this study, we aimed to identify genes linked to neoadjuvant chemotherapy resistance in 62 retrospectively included patients with luminal breast cancer. Whole RNA sequencing of 12 patient biopsies revealed 269 differentially expressed genes in chemoresistant patients. We further validated eight highly correlated genes associated with resistance. Among these, solute carrier family 12 member 1 ( SLC12A1 ) and glutamate ionotropic AMPA type subunit 4 ( GRIA4 ), both implicated in ion transport, showed the strongest association with chemoresistance. Notably, SLC12A1 expression was downregulated, while protein levels of glutamate receptor 4 (GLUR4), encoded by GRIA4 , were elevated in patients with a worse prognosis. Our results suggest a potential link between SLC12A1 gene expression and GLUR4 protein levels with chemoresistance in luminal breast cancer. In particular, GLUR4 protein could serve as a potential target for drug intervention to overcome chemoresistance. |
