Overexpression of SLC6A1 associates with drug resistance and poor prognosis in prostate cancer
Chaojiang Chen,
Zhiduan Cai,
Yangjia Zhuo,
Ming Xi,
Zhuoyuan Lin,
Funeng Jiang,
Zezhen Liu,
Yueping Wan,
Yu Zheng,
Jianxin Li,
Xing Zhou,
Jianguo Zhu,
Weide Zhong
Affiliations
Chaojiang Chen
Guangdong Provincial Institute of Nephrology, Nanfang Hospital, Southern Medical University
Zhiduan Cai
Guangdong Provincial Institute of Nephrology, Nanfang Hospital, Southern Medical University
Yangjia Zhuo
Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology
Ming Xi
Department of Urology, Huadu District People’s Hospital, Southern Medical University
Zhuoyuan Lin
Department of Urology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University
Funeng Jiang
Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology
Zezhen Liu
Guangdong Provincial Institute of Nephrology, Nanfang Hospital, Southern Medical University
Yueping Wan
Department of Urology, Huadu District People’s Hospital, Southern Medical University
Yu Zheng
Department of Urology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University
Jianxin Li
Department of Urology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University
Xing Zhou
Department of Urology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University
Jianguo Zhu
Department of Urology, Guizhou Provincial People’s Hospital, The Affiliated Hospital of Guizhou Medical University
Weide Zhong
Guangdong Provincial Institute of Nephrology, Nanfang Hospital, Southern Medical University
Abstract Background 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. 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. Methods Expression 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. Results Based 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. Conclusions Our 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.
