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在雌激素受体阳性乳腺癌中,CDC20 的表达预示着预后不良和对内分泌治疗缺乏反应。

CDC20 expression in oestrogen receptor positive breast cancer predicts poor prognosis and lack of response to endocrine therapy.

机构信息

Nottingham Breast Cancer Research Centre, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, Nottingham City Hospital, Hucknall Road, Nottingham, NG5 1PB, UK.

Cellular Pathology, Nottingham University Hospitals NHS Trust, Hucknall Road, Nottingham, NG5 1PB, UK.

出版信息

Breast Cancer Res Treat. 2019 Dec;178(3):535-544. doi: 10.1007/s10549-019-05420-8. Epub 2019 Aug 30.

Abstract

PURPOSE

Endocrine therapy is the standard treatment for oestrogen receptor positive (ER+) breast cancer. Despite its efficacy, around half of patients will develop resistance to this treatment and eventually relapse. Identification of effective and reliable biomarkers to predict the efficacy of endocrine therapy is of crucial importance in the management of ER+ breast cancer. Emerging evidence has revealed that the cell division regulator CDC20 exhibits an oncogenic function and plays important roles in tumourigenesis and progression of solid tumours. In this study, we investigated the prognostic and predictive role of CDC20 in early ER+ breast cancer patients.

METHODS

The biological and clinical impact of CDC20 expression was assessed in large clinical annotated cohort of ER+ breast cancer with long-term follow-up at the mRNA level, using METABRIC and KM-Plotter datasets, and the protein level using immunohistochemistry on patients presenting at Nottingham. CDC20 expression was correlated with clinico-pathological parameters, molecular subtypes, clinical outcome and efficacy of endocrine therapy.

RESULTS

High CDC20 mRNA expression was associated with poor clinico-pathological parameters including large tumour size and high tumour grade (P < 0.0001) in patients with ER+ breast cancer. High CDC20 mRNA expression was significantly associated with poor patient outcome (P < 0.0001). Importantly, high CDC20 expression was correlated with poor response to endocrine treatment in patients who treated with hormonal therapy only (P < 0.01). In multivariate analysis, CDC20 mRNA was an independent predictor of poor clinical outcome after treatment with endocrine therapy (P = 0.02).

CONCLUSION

CDC20 is a candidate biomarker for a subgroup of ER+ breast cancer characterised by poor clinical outcome. This study shows that the CDC20 could act as potential predictive biomarker of poor response to endocrine therapy in ER+ breast cancer.

摘要

目的

内分泌治疗是雌激素受体阳性(ER+)乳腺癌的标准治疗方法。尽管其疗效显著,但仍有约半数患者会对此种治疗产生耐药性,最终复发。因此,寻找有效的、可靠的生物标志物来预测内分泌治疗的疗效,对于 ER+乳腺癌的管理至关重要。新出现的证据表明,细胞分裂调节剂 CDC20 具有致癌功能,在实体瘤的发生和进展中发挥重要作用。在本研究中,我们研究了 CDC20 在早期 ER+乳腺癌患者中的预后和预测作用。

方法

通过 METABRIC 和 KM-Plotter 数据集,在具有长期随访的大型临床注释 ER+乳腺癌队列中,从 mRNA 水平评估 CDC20 表达的生物学和临床影响,并在诺丁汉的患者中使用免疫组织化学方法评估 CDC20 蛋白水平。CDC20 表达与临床病理参数、分子亚型、临床结局和内分泌治疗疗效相关。

结果

高 CDC20 mRNA 表达与 ER+乳腺癌患者的不良临床病理参数相关,包括肿瘤较大和肿瘤分级较高(P<0.0001)。高 CDC20 mRNA 表达与患者预后不良显著相关(P<0.0001)。重要的是,在仅接受激素治疗的患者中,高 CDC20 表达与对内分泌治疗的反应不良相关(P<0.01)。在多变量分析中,CDC20 mRNA 是内分泌治疗后临床结局不良的独立预测因子(P=0.02)。

结论

CDC20 是 ER+乳腺癌亚组的候选生物标志物,其临床结局较差。本研究表明,CDC20 可能是 ER+乳腺癌对内分泌治疗反应不良的潜在预测生物标志物。

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