Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Feb 8;9(18):14207-14218.
doi: 10.18632/oncotarget.24453. eCollection 2018 Mar 6.

High expression of SLCO2B1 is associated with prostate cancer recurrence after radical prostatectomy

Tomoaki Terakawa #  1   2 , Eriko Katsuta #  3 , Li Yan  4 , Nitesh Turaga  4 , Kerry-Ann McDonald  3 , Masato Fujisawa  2 , Khurshid A Guru  1 , Kazuaki Takabe  3   5   6   7   8
Affiliations

High expression of SLCO2B1 is associated with prostate cancer recurrence after radical prostatectomy

Tomoaki Terakawa et al. Oncotarget. .

Abstract

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.

Keywords: EMT; OATP; SLCO2B1; prostate cancer; recurrence.

PubMed Disclaimer

Conflict of interest statement

CONFLICTS OF INTEREST There are no potential conflicts of interest to disclose.

Figures

Figure 1
Figure 1. Kaplan–Meier estimate of survival in TCGA PCa patients
DFS (A) and OS (B) in whole TCGA PCa patients. DFS (C) and OS (D) classified by GS in whole TCGA PCa patients. Red line; GS ≤ 6, green line; GS = 7, blue line GS ≥ 8.
Figure 2
Figure 2. Kaplan–Meier estimate of disease-free and overall survival by dichotomized of SLCO2B1 and SLCO1B3 expression in TCGA PCa patients
(A, B) Classified by SLCO2B1 expression level, (C, D) classified by SLCO1B3 expression level. Red line; high expression, blue line; low expression of each genes.
Figure 3
Figure 3. The expression level of SLCO2B1 according to pathological factors in TCGA PCa patients
(A) GS. (B) pathological primary tumor status (pT). (C) surgical margin status.
Figure 4
Figure 4. DFS classified by SLCO2B1 expression level in the subgroups according to GS in TCGA PCa patients
(A) GS ≤ 6, (B) GS = 7, (C) GS ≥ 8. Red line; high expression, blue line; low expression of SLCO2B1.
Figure 5
Figure 5. GSEA between SLCO2B1 high and low expression in patients with GS ≥ 8
Figure 6
Figure 6. EMT related genes expression comparison between SLCO2B1 high and low in patients with GS ≥ 8
See this image and copyright information in PMC

References

    1. Heidenreich A, Bellmunt J, Bolla M, Joniau S, Mason M, Matveev V, Mottet N, Schmid HP, van der Kwast T, Wiegel T, Zattoni F, European Association of U EAU guidelines on prostate cancer. Part 1: screening, diagnosis, and treatment of clinically localised disease. Eur Urol. 2011;59:61–71. doi: 10.1016/j.eururo.2010.10.039. - DOI - PubMed
    1. Roberts WB, Han M. Clinical significance and treatment of biochemical recurrence after definitive therapy for localized prostate cancer. Surg Oncol. 2009;18:268–74. doi: 10.1016/j.suronc.2009.02.004. - DOI - PMC - PubMed
    1. Blute ML, Bergstralh EJ, Iocca A, Scherer B, Zincke H. Use of Gleason score, prostate specific antigen, seminal vesicle and margin status to predict biochemical failure after radical prostatectomy. J Urol. 2001;165:119–25. doi: 10.1097/00005392-200101000-00030. - DOI - PubMed
    1. Nguyen T, Boldt RG, Rodrigues G. Prognostic factors for prostate cancer endpoints following biochemical failure: a review of the literature. Cureus. 2015;7:e238. doi: 10.7759/cureus.238. - DOI - PMC - PubMed
    1. Han M, Partin AW, Pound CR, Epstein JI, Walsh PC. Long-term biochemical disease-free and cancer-specific survival following anatomic radical retropubic prostatectomy. The 15-year Johns Hopkins experience. Urol Clin North Am. 2001;28:555–65. - PubMed