Phosphodiesterase Gene Expression as Independent Outcome Prediction Marker in Localized Prostate Cancer.

Current outcome prediction markers for localized prostate cancer (PCa) are insufficient. The impact of the lipid-modifying Sphingomyelin Phosphodiesterase Acid Like 3B (SMPDL3B) in PCa is unknown. Two cohorts of patients with PCa who underwent radical prostatectomy ( = 40, = 56) and benign prostate hyperplasia (BPH) controls ( = 8, = 11) were profiled for expression with qRT-PCR. Publicly available PCa cohorts (Memorial Sloane Kettering Cancer Centre (MSKCC; = 131, = 29 controls) and The Cancer Genome Atlas (TCGA; = 497, = 53 controls)) served for validation. SMPDL3B's impact on proliferation and migration was analyzed in PC3 cells by siRNA knockdown. In both cohorts, a Gleason score and T stage independent significant overexpression of was seen in PCa compared to BPH ( < 0.001 each). A lower expression of was associated with a shorter overall survival (OS) ( = 0.005) in long term follow-up. A overexpression in PCa tissue was confirmed in the validation cohorts ( < 0.001 each). In the TCGA patients with low SMPDL3B expression, biochemical recurrence-free survival ( = 0.011) and progression-free interval ( < 0.001) were shorter. Knockdown of impaired PC3 cell migration but not proliferation ( = 0.0081). In summary, is highly overexpressed in PCa tissue, is inversely associated with localized PCa prognosis, and impairs PCa cell migration.