Abstract
BackgroundSolute Carrier Family 6 Member 1 (SLC6A1) has been identified as a cancer-promoting gene in various human cancers, such as clear cell renal cell carcinoma and ovarian cancer. However, its roles in prostate cancer (PCa) has not been fully elucidated. The aim of this study was to investigate the expression and clinical significance of SLC6A1 in PCa tissues and its effect on drug resistance to docetaxel in PCa.MethodsExpression patterns of SLC6A1 protein in PCa tissues were examined by immunohistochemistry based on Tissue microarray. Associations of SLC6A1 protein expression with various clinicopathological features and patients’ prognosis of PCa were also statistically evaluated based on TCGA data. Roles of SLC6A1 deregulation in prostate carcinogenesis and drug resistance was further determined in vitro and in vivo experiments.ResultsBased on TCGA Dataset, SLC6A1 expression was markedly higher in patients with high Gleason score, advanced clinical stage and positive biochemical recurrence than those with control features (all P < 0.05). Both unvariate and multivariate analyses demonstrated that SLC6A1 expression was significantly associated with biochemical recurrence-free survival in PCa patients. In addition, enforced expression of SLC6A1 effectively promoted cell proliferation, migration and invasion of PCa cells in vitro. Moreover, the inhibition of SLC6A1 suppressed the tumor growth in vivo. Additionally, immunohistochemical notches of PCNA and MMP-9 in the low-expression cluster were pointedly lower compared to those of NC group. Finally, the cell viability revealed that the overexpression of SLC6A1 obviously promoted the PCa cell resistant to docetaxel (DTX), and the transplanted tumor in the overexpression group had no significant reduction compared with the untreated group.ConclusionsOur data suggest that SLC6A1 overexpression may be associated with aggressive progression and short biochemical recurrence-free survival of PCa, and may be related to the resistance to docetaxel therapy.
Highlights
Solute Carrier Family 6 Member 1 (SLC6A1) has been identified as a cancer-promoting gene in various human cancers, such as clear cell renal cell carcinoma and ovarian cancer
It is of great clinical significance to identify molecular biomarkers which can predict the patients’ response to the treatment of docetaxel, in order to assist in screening the responsive prostate cancer patients to docetaxel and potentially benefit individualized therapy of prostate cancer in a daily clinical setting
SLC6A1 overexpression significantly associates with aggressive progression and poor prognosis in patients with prostate cancer As shown in Fig. 1a-b, positive immunostaining of SLC6A1 protein was localized in the cell cytoplasm of prostate cancer tissues
Summary
Solute Carrier Family 6 Member 1 (SLC6A1) has been identified as a cancer-promoting gene in various human cancers, such as clear cell renal cell carcinoma and ovarian cancer. The aim of this study was to investigate the expression and clinical significance of SLC6A1 in PCa tissues and its effect on drug resistance to docetaxel in PCa. Prostate cancer, the fourth common malignancy in Europe [1], is the largest annual increase (26%) of men and the second (9%) in deaths in the United States [2]. Despite of the effective treatments, including castration, radical prostatectomy, and high-dose radiotherapy, 20–30% of patients with prostate cancer may recur biochemically within 5–10 years and progress to hormone-resistant prostate cancer (CRPC) [4,5,6]. It is of great clinical significance to identify molecular biomarkers which can predict the patients’ response to the treatment of docetaxel, in order to assist in screening the responsive prostate cancer patients to docetaxel and potentially benefit individualized therapy of prostate cancer in a daily clinical setting
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