ASPM is a predictor of overall survival and has therapeutic potential in endometrial cancer

Am J Transl Res. 2020 May 15;12(5):1942-1953. eCollection 2020.

Abstract

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 (P<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.

Keywords: ASPM; Wnt/β-catenin; endometrial carcinoma; prognosis.