ArticleCancer cell international2023
GAD1 contributes to the progression and drug resistance in castration resistant prostate cancer.
Article in Cancer cell international, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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6 citing papers in PubMed.
- [Comparison of clinical outcomes between radical prostatectomy and permanent prostate brachytherapy in patients with oligometastatic prostate cancer: A propensity score-matched study].Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences · 2026Article
- Molecular Characteristics, Potential Mechanisms, and Prognostic Gene Model of Younger Female Patients With Gastric Cancer.Cancer reports (Hoboken, N.J.) · 2026Article
- Fatty acid metabolism related gene MECR contributes to the progression of prostate cancer.Cancer cell international · 2025Article
- Potential role of P4HB in the tumor microenvironment and its clinical prognostic value: a comprehensive pan-cancer analysis and experimental validation with a focus on KIRC.Cancer cell international · 2025Article
- Article
- Co-targeting SKP2 and KDM5B inhibits prostate cancer progression by abrogating AKT signaling with induction of senescence and apoptosis.The Prostate · 2024Article
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Abstract
backgroundProstate cancer is currently the second most lethal malignancy in men worldwide due to metastasis and invasion in advanced stages. Studies have revealed that androgen deprivation therapy can induce stable remission in patients with advanced prostate cancer, although most patients will develop castration-resistant prostate cancer (CRPC) in 1-2 years. Docetaxel and enzalutamide improve survival in patients with CRPC, although only for a short time, eventually patients develop primary or secondary resistance, causing disease progression or biochemical relapse.
methodsThe gene expression profiles of docetaxel-sensitive or -resistant prostate cancer cell lines, namely GSE33455, GSE36135, GSE78201, GSE104935, and GSE143408, were sequentially analyzed for differentially expressed genes and progress-free interval significance. Subsequently, the overall survival significance and clinic-pathological features were analyzed by the R package. The implications of hub genes mutations, methylation in prostate cancer and the relationship with the tumor immune cell infiltration microenvironment were assessed with the help of cBioPortal, UALCAN and TISIDB web resources. Finally, effects of the hub genes on the progression and drug resistance in prostate cancer were explored using reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry, cell phenotype, and drug sensitivity.
resultGlutamate decarboxylase 1 (GAD1) was tentatively identified by bioinformatic analysis as an hub gene for the development of drug resistance, including docetaxel and enzalutamide, in prostate cancer. Additionally, GAD1 expression, mutation and methylation were significantly correlated with the clinicopathological features and the tumor immune microenvironment. RT-PCR, immunohistochemistry, cell phenotype and drug sensitivity experiments further demonstrated that GAD1 promoted prostate cancer progression and decreased the therapeutic effect of docetaxel or enzalutamide.
conclusionThis research confirmed that GAD1 was a hub gene in the progression and development of drug resistance in prostate cancer. This helped to explain prostate cancer drug resistance and provides new immune-related therapeutic targets and biomarkers for it.
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