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BMC Cancer
Published in: BMC Cancer 1/2020

01-12-2020 | Prostate Cancer | Research article

Overexpression of SLC6A1 associates with drug resistance and poor prognosis in prostate cancer

Authors: 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

Published in: BMC Cancer | Issue 1/2020

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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.
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Metadata
Title
Overexpression of SLC6A1 associates with drug resistance and poor prognosis in prostate cancer
Authors
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
Publication date
01-12-2020
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2020
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-020-06776-7

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