异常纺锤体样微管相关蛋白（ASPM）是子宫内膜癌总生存期的一个预测指标，并且具有治疗潜力。
ASPM is a predictor of overall survival and has therapeutic potential in endometrial cancer.
作者信息
Zhou Jing-Wei, Wang Hui, Sun Wei, Han Nan-Nan, Chen Liang
机构信息
Department of Gynaecology, Jiangsu Province Hospital Nanjing 210000, P. R. China.
出版信息
Am J Transl Res. 2020 May 15;12(5):1942-1953. eCollection 2020.
BACKGROUND
Endometrial carcinoma (EC) is one of the most common cancers in women, and its pathogenesis is complex. Abnormal spindle microtubule assembly (ASPM) is highly expressed in a variety of cancers and is related to poor clinical prognosis and recurrence. However, the role of ASPM in EC is still unclear. Our study was conducted to investigate the association of ASPM with tumour progression and prognosis in EC.
METHODS
The expression level of ASPM in EC patients was analysed by using the TCGA database and by using immunohistochemistry (IHC) to analyse EC patient samples. The relationship between ASPM expression and clinicopathological variables was analysed by the chi-square test. Survival curves were analysed by Kaplan-Meier survival analysis and log-rank test. Univariate and multivariate Cox regression analyses were performed to measure the prognosis of EC. The effects of ASPM on the proliferation, invasion and metastasis of EC cells (HEC-1A and Ishikawa) were analysed by MTT and Transwell assays. The effect of ASPM on the Wnt/β-catenin signalling pathway was detected by Western blotting.
RESULTS
ASPM was highly overexpressed in EC. Overexpression of ASPM was related to significantly worse overall survival (<0.05) in EC patients. Univariate and multivariate Cox regression analyses suggested that upregulation of ASPM was related to poor prognosis in EC. Knockdown of ASPM inhibited the proliferation, migration and invasion of EC cells. ASPM knockdown suppressed the Wnt/β-catenin signalling pathway, while β-catenin overexpression reversed the effect of shASPM on cell activity.
CONCLUSIONS
ASPM acts as an independent predictor of clinical prognosis and serves as a potential target gene for EC therapy.
背景
子宫内膜癌（EC）是女性最常见的癌症之一，其发病机制复杂。异常纺锤体微管组装蛋白（ASPM）在多种癌症中高表达，且与临床预后不良及复发相关。然而，ASPM在EC中的作用仍不清楚。我们开展本研究以探讨ASPM与EC肿瘤进展及预后的关系。
方法
利用TCGA数据库分析EC患者中ASPM的表达水平，并采用免疫组织化学（IHC）分析EC患者样本。通过卡方检验分析ASPM表达与临床病理变量之间的关系。采用Kaplan-Meier生存分析和对数秩检验分析生存曲线。进行单因素和多因素Cox回归分析以评估EC的预后。通过MTT和Transwell实验分析ASPM对EC细胞（HEC-1A和Ishikawa）增殖、侵袭和转移的影响。通过蛋白质免疫印迹法检测ASPM对Wnt/β-连环蛋白信号通路的影响。
结果
ASPM在EC中高度过表达。ASPM过表达与EC患者总体生存率显著降低相关（<0.05）。单因素和多因素Cox回归分析表明，ASPM上调与EC预后不良相关。敲低ASPM可抑制EC细胞的增殖、迁移和侵袭。敲低ASPM可抑制Wnt/β-连环蛋白信号通路，而β-连环蛋白过表达可逆转shASPM对细胞活性的影响。
结论
ASPM是临床预后的独立预测指标，可作为EC治疗的潜在靶基因。
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