High expression of SLCO2B1 is associated with prostate cancer recurrence after radical prostatectomy
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Tomoaki Terakawa1,2,*, Eriko Katsuta3,*, Li Yan4, Nitesh Turaga4, Kerry-Ann McDonald3, Masato Fujisawa2, Khurshid A. Guru1 and Kazuaki Takabe3,5,6,7,8
1Department of Urology, Roswell Park Cancer Institute, Buffalo, NY, USA
2Department of Urology, Kobe University Graduate School of Medicine, Kobe, Japan
3Department of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, NY, USA
4Department of Biostatistics and Bioinformatics, Roswell Park Cancer Institute, NY, USA
5Department of Surgery, University at Buffalo, Jacobs School of Medicine and Biomedical Sciences, The State University of New York Buffalo, NY, USA
6Department of Breast Surgery and Oncology, Tokyo Medical University, Tokyo, Japan
7Department of Surgery, Yokohama City University, Yokohama, Japan
8Department of Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
*These authors contributed equally to this work
Kazuaki Takabe, email: [email protected]
Keywords: prostate cancer; SLCO2B1; recurrence; EMT; OATP
Received: September 11, 2017 Accepted: February 01, 2018 Epub: February 08, 2018 Published: March 06, 2018
Solute carrier organic anion (SLCO) gene families encode organic anion transport proteins, which are transporters that up-take a number of substrates including androgens. Among them, high expression of SLCO2B1 is known to associate with the resistance to androgen deprivation therapy in prostate cancer (PCa). We hypothesized that high expression of SLCO genes enhances PCa progression by promoting the influx of androgen. Here, we demonstrated the impact of the expression levels of SLCO2B1 on prognosis in localized PCa after radical prostatectomy (RP) utilizing 494 PCa cases in The Cancer Genome Atlas (TCGA). SLCO2B1 high expression group showed significantly worse Disease-free survival (DFS) after RP (p = 0.001). The expression level of SLCO2B1 was significantly higher in advanced characteristics including Gleason Score (GS ≤ 6 vs GS = 7; p = 0.047, GS = 7 vs GS ≥ 8; p = 0.002), pathological primary tumor (pT2 vs pT3/4; p < 0.001), and surgical margin status (positive vs negative; p = 0.013), respectively. There was a significant difference in DFS between these two groups only in GS ≥ 8 patients (p = 0.006). Multivariate analysis demonstrated that only SLCO2B1 expression level was an independent predictor for DFS after RP in GS ≥ 8. SLCO2B1 high expressed tumors in GS ≥ 8 not only enriched epithelial mesenchymal transition (EMT) related gene set, (p = 0.027), as well as Hedgehog (p < 0.001), IL-6/JAK/STAT3 (p < 0.001), and K-ras signaling gene sets (p < 0.001), which are known to promote EMT, but also showed higher expression of EMT related genes, including N-cadherin (p = 0.024), SNAIL (p = 0.001), SLUG (p = 0.001), ZEB-1 (p < 0.001) and Vimentin (p < 0.001). In conclusion, PCa with high expression of SLCO2B1 demonstrated worse DFS, which might be due to accelerated EMT.
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