Construction and validation of a lysine beta hydroxybutyrylation related molecular model for predicting biochemical...

The role of protein lysine β-hydroxybutyrylation (Kbhb) in the progression of PCa remains uncertain. We aimed to construct a novel Kbhb related molecular model for predicting biochemical recurrence-free survival (BCRFS) of prostate cancer (PCa) patients and performed preliminary experimental validations of role of RPS10 in the progression and docetaxel resistance of PCa. The clinical and transcriptome data of PCa from TCGA and GEO database were downloaded for bioinformatics analysis. We conducted multivariate Cox regression analysis to construct a novel Kbhb related molecular model for predicting BCRFS. To evaluate the validity of the model, both internal and external validations were carried out. Preliminary experimental validations were performed to verify the biological functions of RPS10 in PCa progression and docetaxel resistance. We identified a total of 63 differentially expressed Kbhb related genes and three Kbhb related molecular clusters. These three clusters showed significantly different clinicopathological features and prognosis. Most importantly, we constructed a novel Kbhb related molecular model for predicting the BCRFS of PCa. The difference in BCRFS between high and low-risk was statistically significant in training cohort (P < 0.001), testing cohort (P = 0.005), whole TCGA cohort (P < 0.001), validating cohort (P = 0.002). The area under time-dependent ROC curve (AUC) were 0.817, 0.701, 0.758, and 0.744 of the four cohorts above respectively. Preliminary experiment revealed that RPS10 and its K107bhb promote the proliferation and docetaxel resistance of PCa cells.