Exploration and Identification of Potential Therapeutic Targets and Biomarkers for Docetaxel Resistant Prostate Cancer
Abstract Background: Prostate cancer has become the third most common cancer, and the death rate of advanced patients due to metastasis and invasion is high. Approximately 40% to 50% of castration resistant prostate cancer responding to docetaxel did not show a substantial and sustained prostate specific antigen decline, and the median response duration was limited to 6 to 9 months.Objective: To understand the pathogenesis of docetaxel-resistant prostate cancer (DRPC), and to search for prognostic markers and new therapeutic targets.Methods: RNA sequencing data of GSE36135 and GSE33455 from the Gene Expression Synthesis Database were used to search for co-expressed genes. Univariate and multivariate Cox regression analyses were performed to identify independent prognostic factors, which were validated by expression and survival analyses. Subsequently, their ability to jointly predict patient prognosis was evaluated. Then, the lasso Cox regression model was established to evaluate the correlation of DEGs with immune score, ferroptosis, methylation, and OCLR score. And predicted for targeted small molecule drugs and validated the effect of small molecule drugs.Results: EZH2 and SRC were identified as potential therapeutic targets and effective prognostic markers for docetaxel-resistant prostate cancer, and were found to be significantly associated with the immune score, ferroptosis, methylation, and OCLR score. Targeted small molecule drugs were predicted and validated for EZH2 and SRC.Conclusions: This study helps to fully explain the mechanism of docetaxel-resistant prostate cancer formation and provides new immune-related therapeutic targets and biomarkers for it. Preliminary exploration of the effects of docetaxel in combination with urapidil or roxithromycin in prostate cancer cells