SLC6A1 的过表达与前列腺癌的耐药性和不良预后相关。
Overexpression of SLC6A1 associates with drug resistance and poor prognosis in prostate cancer.
机构信息
Guangdong Provincial Institute of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
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, Guangzhou, 510180, China.
出版信息
BMC Cancer. 2020 Apr 6;20(1):289. doi: 10.1186/s12885-020-06776-7.
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.
背景
溶质载体家族 6 成员 1（SLC6A1）已被确定为多种人类癌症（如透明细胞肾细胞癌和卵巢癌）中的致癌基因。然而，其在前列腺癌（PCa）中的作用尚未完全阐明。本研究旨在探讨 SLC6A1 在 PCa 组织中的表达及其对 PCa 多西紫杉醇耐药性的影响。
方法
基于组织微阵列的免疫组织化学方法检测 SLC6A1 蛋白在 PCa 组织中的表达模式。基于 TCGA 数据，统计评估 SLC6A1 蛋白表达与各种临床病理特征和 PCa 患者预后的相关性。进一步通过体外和体内实验确定 SLC6A1 失调在前列腺癌发生和耐药中的作用。
结果
基于 TCGA 数据集，高 Gleason 评分、晚期临床分期和生化复发阳性的患者 SLC6A1 表达明显高于对照组（均 P<0.05）。单变量和多变量分析均表明 SLC6A1 表达与 PCa 患者的生化无复发生存显著相关。此外，SLC6A1 的强制表达有效地促进了 PCa 细胞的体外增殖、迁移和侵袭。此外，体内抑制 SLC6A1 抑制了肿瘤的生长。此外，低表达簇中的 PCNA 和 MMP-9 的免疫组化缺口明显低于 NC 组。最后，细胞活力显示 SLC6A1 的过表达明显促进了 PCa 细胞对多西紫杉醇（DTX）的耐药性，过表达组的移植瘤与未处理组相比没有明显减少。
结论
我们的数据表明，SLC6A1 过表达可能与 PCa 的侵袭性进展和生化无复发生存时间短有关，并且可能与多西紫杉醇治疗耐药有关。
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