Autophagy induced by overexpression of DCTPP1 promotes tumor progression and predicts poor clinical outcome in prostate cancer

Abstract

Although dCTP pyrophosphatase 1 (DCTPP1) has been reported to be associated with poor clinical outcomes in various cancers, whether it plays an important role in prostate cancer (PCa) remains unclear. In this study, an immunohistochemical assay showed the protein expression level of DCTPP1 was significantly higher in PCa tissues than in non-cancerous tissues. Moreover, DCTPP1 was upregulated at both protein and mRNA levels in the PCa tissues from high Gleason score patients versus low Gleason score patients. The analysis of The Cancer Genome Atlas RNA-seq data suggested that upregulation of DCTPP1 was inversely correlated with biochemical recurrence free survival and overall survival. The roles of DCTPP1 in tumor progression and autophagy were further validated through cells invasion, migration, apoptosis and proliferation assays in vitro, as well as EMT and autophagy assays in vivo. Advanced bioinformatics analysis identified the evidence supporting the promotional role of DCTPP1 in tumor progression associated with autophagy. We conclude that DCTPP1 may play an important role in PCa progression associated with high autophagy. Overexpression of DCTPP1 may server as a biomarker for predicting poor BCR-free survival and overall survival for PCa patients.

Keywords: Autophagy; Biochemical recurrence free-survival; Overall survival; Prostate cancer; dCTP pyrophosphatase 1.