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KIF20A 作为不同亚型乳腺癌的预后生物标志物和治疗靶点的特征。

Characterization of KIF20A as a prognostic biomarker and therapeutic target for different subtypes of breast cancer.

机构信息

Department of Medical Oncology and Cancer Center, Shiga University of Medical Science, Otsu, Shiga 520‑2192, Japan.

Department of Pathology, Kanagawa Cancer Center, Yokohama, Kanagawa 241‑8515, Japan.

出版信息

Int J Oncol. 2020 Jul;57(1):277-288. doi: 10.3892/ijo.2020.5060. Epub 2020 May 7.

Abstract

The aim of the present study was to identify novel prognostic biomarkers and therapeutic targets for breast cancer; thus, genes that are frequently overexpressed in several types of breast cancer were screened. Kinesin family member 20A (KIF20A) was identified as a candidate molecule during this process. Immunohistochemical staining performed using tissue microarrays from 257 samples of different breast cancer subtypes revealed that KIF20A was expressed in 195 (75.9%) of these samples, whereas it was seldom expressed in normal breast tissue. KIF20A protein was expressed in all types of breast cancer observed. However, it was more frequently expressed in human epidermal growth factor receptor 2 (HER2)‑positive and triple‑negative breast cancer than in the luminal type. Moreover, KIF20A expression was significantly associated with the poor prognosis of patients with breast cancer. A multivariate analysis indicated that KIF20A expression was an independent prognostic factor for patients with breast cancer. The suppression of endogenous KIF20A expression using small interfering ribonucleic acids or via treatment with paprotrain, a selective inhibitor of KIF20A, significantly inhibited breast cancer cell growth through cell cycle arrest at the G2/M phase and subsequent mitotic cell death. These results suggest that KIF20A is a candidate prognostic biomarker and therapeutic target for different types of breast cancer.

摘要

本研究旨在鉴定乳腺癌的新型预后生物标志物和治疗靶点;因此,筛选了在几种乳腺癌中频繁过表达的基因。在这个过程中,发现驱动蛋白家族成员 20A(KIF20A)是一个候选分子。使用来自 257 个不同乳腺癌亚型的组织微阵列进行免疫组织化学染色显示,KIF20A 在这些样本中的 195 个(75.9%)中表达,而在正常乳腺组织中很少表达。在观察到的所有类型的乳腺癌中均表达 KIF20A 蛋白。然而,它在人表皮生长因子受体 2(HER2)阳性和三阴性乳腺癌中的表达频率高于管腔型。此外,KIF20A 表达与乳腺癌患者的不良预后显著相关。多变量分析表明,KIF20A 表达是乳腺癌患者的独立预后因素。使用小干扰核糖核酸或通过使用 KIF20A 的选择性抑制剂 paprotrain 抑制内源性 KIF20A 表达,通过细胞周期阻滞在 G2/M 期和随后的有丝分裂细胞死亡,显著抑制乳腺癌细胞生长。这些结果表明,KIF20A 是不同类型乳腺癌的候选预后生物标志物和治疗靶点。

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