Co-expression of Twist and Snai1: predictor of poor prognosis and biomarker of treatment resistance in untreated prostate cancer

Background: Prostate cancer (PCa) remains one of the most complex tumors in men. The assessment of gene expression is expected to have a profound impact on cancer diagnosis, prognosis, and treatment decisions. The aim of this study was to determine the utility of the epithelial-mesenchymal transition (EMT) transcription factors Twist and Snai1 in the treatment of naïve prostate cancer.

Methods and results: We analyzed formalin-fixed paraffin-embedded (FFPE) prostate tissues from 108 PCa patients and 20 control biopsies using real-time quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and 2^-ΔΔCt methods for Twist and Snail gene expression. The expression of Twist and Snai1 mRNA was significantly overexpressed in primary tissues of PCa patients compared with controls using ROC curve. Statistical analysis showed that the mRNAs of these two genes expression Snai1 and Twist were positively correlated with tumor development and prognostic parameters as Gleason score (p < 0.001; r = 0.707) and (p < 0.001; r = 0.627) respectively. The results of Kaplan-Meier analysis showed that mRNA expression of Snai1 and Twist genes expression were significant predictors of poor overall survival (OS) (Log rank p < 0.001) and progression-free survival (PFS) of patients (Log rank p < 0.001). Furthermore, our results showed that the expression of Snai1 and Twist genes expression in primary tissues of PCa patients could predict resistance to androgen deprivation therapy (p < 0.001) and resistance to the acidic drugs abiraterone or enzalutamide (p < 0.001). However, these two transcription factors failed to predict taxanes resistance at the time of diagnosis (p > 0.05).

Conclusion: These results suggest that Snai1 and Twist are overexpressed during the onset and progression of PCa malignancies and may be theranostic markers of resistance to ADT, abiraterone, or enzalutamide therapy.