T. TERAKAWA1,2, E. Katsuta3, M. Fujisawa2, K. Guru1, K. Takabe3 1Roswell Park Cancer Institute,Urology,Buffalo, NY, USA 2Kobe University,Urology,Kobe, , Japan 3Roswell Park Cancer Institute,Surgical Oncology,Buffalo, NY, USA
Introduction:
Solute carrier organic anion (SLCO) genes encode organic anion transport proteins, which is a family of transport proteins that influx number of substrates into the cells including androgens. Among them, high expression of SLCO2B1 has been shown to be associated with the resistance to androgen deprivation therapy and with the prognosis of the patients with hormone sensitive prostate cancer. Here, we hypothesized that the high expression of SLCO2B1 in human prostate cancer may increase influx of androgens to remaining undetectable dormant cancer cells thus is associated with worse disease-free survival after radical prostatectomy.
Methods:
Clinical and RNA-seq data were all obtained from the Cancer Genome Atlas (TCGA). Patients were classified as either high or low expression of SLCO2B1 by the mean value. Overall survival (OS) and disease-free survival (DFS) were compared between high and low expression group in whole cohort, as well as subgroups based upon Gleason score (GS≤6, =7 or ≥8). Gene set enrichment analysis (GSEA) were conducted between high and low expression group.
Results:
Of all patients, 193 and 305 patients were classified as SLCO2B1 high and low expression group, respectively. The patients with high expression of SLCO2B1 were found to have more aggressive cancer characteristics, including high Gleason score (p<0.001), higher T stage (p<0.001), and positive surgical margin (p=0.011). Among all patients, 5-year OS and DFS were 97.8% and 71.2%, respectively. High expression group showed significantly worse DFS after radical prostatectomy (5-year DFS rate: 60.3% vs 78.7%, p=0.026), whereas there was no significant difference in overall survival between these two groups (5-year OS rate: 99.3% vs 96.8%, p=0.923). The patients with higher Gleason score had significantly higher levels of SLCO2B1 expression (GS≤6, vs GS=7; p=0.045, GS=7 vs GS≥8; p=0.002). Significant difference in DFS between high and low expression groups were only observed in the patients with GS≥8 (5-year DFS rate: 38.6% vs 70%, p=0.005), and not in the patients with GS≤7 (GS≤6; p=0.640, GS=7; p=0.923). GSEA demonstrated that in the high expression group of SLCO2B1 enriched KRAS signaling, epithelial mesenchymal transition (EMT) and TGF beta signaling related genes.
Conclusion:
High expression of SLCO2B1 in the prostate cancer patients associated with the aggressive cancer characteristics and recurrence after radical prostatectomy. Furthermore, the higher recurrence rate of the patients with high expression of SLCO2B1 may be able to be explained by its metastatic potential with up-regulated EMT signaling by KRAS and TGF beta pathways.