Association of SLC12A1 and GLUR4 Ion Transporters with Neoadjuvant Chemoresistance in Luminal Locally Advanced Breast Cancer
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Association of SLC12A1 and GLUR4 Ion Transporters with Neoadjuvant Chemoresistance in Luminal Locally Advanced Breast Cancer. / Justo-Garrido, Montserrat; López-Saavedra, Alejandro; Alcaraz, Nicolás; Cortés-González, Carlo C.; Oñate-Ocaña, Luis F.; Caro-Sánchez, Claudia Haydee Sarai; Castro-Hernández, Clementina; Arriaga-Canon, Cristian; Díaz-Chávez, José; Herrera, Luis A.
In: International Journal of Molecular Sciences, Vol. 24, No. 22, 16104, 2023.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Association of SLC12A1 and GLUR4 Ion Transporters with Neoadjuvant Chemoresistance in Luminal Locally Advanced Breast Cancer
AU - Justo-Garrido, Montserrat
AU - López-Saavedra, Alejandro
AU - Alcaraz, Nicolás
AU - Cortés-González, Carlo C.
AU - Oñate-Ocaña, Luis F.
AU - Caro-Sánchez, Claudia Haydee Sarai
AU - Castro-Hernández, Clementina
AU - Arriaga-Canon, Cristian
AU - Díaz-Chávez, José
AU - Herrera, Luis A.
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
KW - chemoresistance
KW - ion transport
KW - locally advanced
KW - luminal breast cancer
KW - neoadjuvant chemotherapy
U2 - 10.3390/ijms242216104
DO - 10.3390/ijms242216104
M3 - Journal article
C2 - 38003293
AN - SCOPUS:85177806183
VL - 24
JO - International Journal of Molecular Sciences (Online)
JF - International Journal of Molecular Sciences (Online)
SN - 1661-6596
IS - 22
M1 - 16104
ER -
ID: 375205653