A novel prognostic risk score associated with resistance to docetaxel chemotherapy for predicting biochemical recurrence-free survival in patients with prostate cancer.

Objective: To identify molecular clusters and develop a novel prognostic risk score associated with resistance to docetaxel chemotherapy for predicting biochemical recurrence free survival (BCRFS) and tumor immune microenvironment of prostate cancer (PCa).

Materials And Methods: We obtained the clinical and transcriptome data of PCa from TCGA and GEO database. Univariate and multivariate Cox regression analysis were used to establish a novel prognostic risk score associated with resistance to docetaxel chemotherapy for predicting BCRFS. To evaluate the validity of the risk score, both internal and external validations were carried out. Preliminary in-vivo and in-vitro experimental validations were performed to verify the biological functions of NOG in PCa docetaxel resistance.

Results: After screening 67 docetaxel resistance related differentially expressed gene (DEGs), we identified three docetaxel resistance-related clusters with significantly different BCRFS, immune cell infiltration, and PD-L1 expression. More importantly, a novel docetaxel resistance-related prognostic risk score was constructed. In training, testing, and validating cohorts, the BCRFS of the patients with high-risk scores was considerably lower. The AUCs for the three cohorts were 0.767, 0.714, and 0.719, respectively. Subgroup analysis suggested that the risk score has a strong clinical value in the TIII-IV N0 or clusters 1-2 PCa patients. The expression of the NOG was significantly elevated in docetaxel-resistant PCa cells compared to the normal strain. The knockdown of the NOG reduced the IC50 of docetaxel of docetaxel-resistant PCa cells and the overexpression of NOG increased the IC50 of docetaxel and promoted the colony formation ability under docetaxel treatment of DU145 and PC-3 cells. In vivo tumorigenesis assay revealed that the overexpression of NOG could promote the tumorigenesis of PCa under docetaxel treatment.

Conclusions: We successfully identified a total of 67 docetaxel resistance related DEGs. A novel prognostic risk score associated with resistance to docetaxel chemotherapy of PCa was developed and validated, which performed well in predicting the BCRFS of PCa. High expression of NOG could promote the docetaxel resistance of PCa.