@misc{10481/106460,
year = {2025},
month = {8},
url = {https://hdl.handle.net/10481/106460},
abstract = {Background/Objectives: Androgen deprivation therapy (ADT) is widely used to manage
prostate cancer (PC), but the emergence of treatment resistance remains a major clinical
challenge. Although the GST family has been implicated in drug resistance, the specific
role of GSTM5 remains poorly understood. This study investigates whether GSTM5, alone
or in combination with clinical variables, can improve patient stratification based on the
risk of early treatment resistance. Methods: In silico analyses were performed to examine GSTM5’s role in protein interactions, molecular pathways, and gene expression.
The rs3768490 polymorphism was genotyped in 354 patients with PC, classified by ADT
response. Descriptive analysis and logistic regression models were applied to evaluate
associations between genotype, clinical variables, and ADT response. GSTM5 expression related to the rs3768490 genotype and ADT response was also analyzed in 129 prostate tissue
samples. Results: The T/T genotype of rs3768490 was significantly associated with a lower
likelihood of early ADT resistance in both individual (p = 0.0359, Odd Ratios (OR) = 0.18)
and recessive models (p = 0.0491, OR = 0.21). High-risk classification according to D’Amico
was strongly associated with early progression (p < 0.0004; OR > 5.4). Combining genotype and clinical risk improved predictive performance, highlighting their complementary
value in stratifying patients by treatment response. Additionally, GSTM5 expression was
slightly higher in T/T carriers, suggesting a potential protective role against ADT resistance. Conclusions: The T/T genotype of rs3768490 may protect against ADT resistance by
modulating GSTM5 expression in PC. These preliminary findings highlight the potential of
integrating genetic biomarkers into clinical models for personalized treatment strategies,
although further studies are needed to validate these observations.},
organization = {Ministry of Science and Innovation (grant number PRED2020-094013)},
organization = {Ministry of Education (grant number FPU21/05808;  FPU20/06611)},
organization = {Proyectos en Salud FIBAO - Junta de Andalucía (PIP-0043-2022)},
publisher = {MDPI},
keywords = {castration-resistant prostate cancer},
keywords = {GSTM5},
keywords = {biomarker},
title = {GSTM5 as a Potential Biomarker for Treatment Resistance in Prostate Cancer},
doi = {10.3390/ biomedicines13081872},
author = {Porras-Quesada, Patricia and Chica-Redecillas, Lucía and Álvarez-González, Beatriz and Gutiérrez-Tejero, Francisco and Arrabal-Martín, Miguel and Ríos-Pelegrina, Rosa and Martínez-González, Luis Javier and Álvarez-Cubero, Maria Jesus and Vázquez-Alonso, Fernando},
}