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分泌型簇蛋白 (sCLU) 的过度表达与原发性乳腺癌对术前新辅助化疗的耐药性有关。

Secretory clusterin (sCLU) overexpression is associated with resistance to preoperative neoadjuvant chemotherapy in primary breast cancer.

机构信息

The center of Breast disease, the Affiliated Hospital of Qingdao Medical College, Qingdao University, Qingdao, R.P. China.

出版信息

Eur Rev Med Pharmacol Sci. 2013 May;17(10):1337-44.

PMID:23740447
Abstract

OBJECTIVES

Preoperative chemotherapy is often used in patients with locally advanced breast cancer. However, commonly used clinical and pathological parameters are poor predictors of response to this type of therapy. The secreted form of the CLU protein (sCLU) is a glycosylated protein of 76-80 kDa. It has become increasingly clear that in most cells sCLU is a stress-associated cytoprotective protein that is upregulated by various apoptotic triggers. Furthermore, sCLU confers resistance by some unknown mechanism when overexpressed. The purpose of the present study was to examine the sCLU proteins as predictors of clinical outcome and response to chemotherapy in locally advanced breast cancer.

PATIENTS AND METHODS

The expression levels of sCLU was determined by immunohistochemistry before preoperative chemotherapy in 72 patients with locally advanced breast cancer. All patients were treated with cyclophosphamide/doxorubicin/5-FU(CAF) and some patients received additional treatment with docetaxel. Expression data were compared with patients' clinical and pathological features, clinical outcome, and response to chemotherapy.

RESULTS

The results showed sCLU expression before preoperative chemotherapy was inversely related to the tumor size, expression of estrogen and progesterone receptors. High preoperative expression of sCLU was associated with resistance to CAF therapy, but not with resistance to docetaxel.

CONCLUSIONS

We, therefore, suggested sCLU expression may be a useful marker for predicting response to preoperative chemotherapy and clinical outcome in patients with locally advanced breast cancer.

摘要

目的

术前化疗常用于局部晚期乳腺癌患者。然而,常用的临床和病理参数是预测此类治疗反应的不良指标。CLU 蛋白的分泌形式(sCLU)是一种 76-80 kDa 的糖基化蛋白。越来越明显的是,在大多数细胞中,sCLU 是一种与应激相关的细胞保护性蛋白,可被各种凋亡触发物上调。此外,sCLU 通过未知机制过表达时赋予耐药性。本研究旨在探讨 sCLU 蛋白作为局部晚期乳腺癌临床结局和化疗反应的预测因子。

患者和方法

在 72 例局部晚期乳腺癌患者术前化疗前,通过免疫组织化学法测定 sCLU 的表达水平。所有患者均接受环磷酰胺/多柔比星/5-FU(CAF)治疗,部分患者接受多西紫杉醇辅助治疗。将表达数据与患者的临床病理特征、临床结局和化疗反应进行比较。

结果

结果表明,术前化疗前 sCLU 的表达与肿瘤大小、雌激素和孕激素受体的表达呈负相关。术前 sCLU 高表达与 CAF 治疗耐药相关,但与多西紫杉醇耐药无关。

结论

因此,我们认为 sCLU 表达可能是预测局部晚期乳腺癌患者术前化疗反应和临床结局的有用标志物。

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