乙醛脱氢酶1与乳腺癌耐药蛋白在乳腺癌中的表达及相关性研究

doi:10.3969/j.issn.1007-3969.2014.03.004

中国癌症杂志 ›› 2014, Vol. 24 ›› Issue (3): 175-181.doi: 10.3969/j.issn.1007-3969.2014.03.004

乙醛脱氢酶1与乳腺癌耐药蛋白在乳腺癌中的表达及相关性研究

王兴¹,姜真¹,孙长岗²

1.山东省禹城市人民医院肿瘤内科，山东德州 251200；
2.潍坊市中医院肿瘤中心，山东潍坊 261041

出版日期:2014-03-31 发布日期:2014-04-01
通信作者: 姜真　E-mail:dzjiangzhen@163.com
基金资助:
国家自然科学基金项目(No：81273987)

Research of expression of aldehyde dehydrogenase 1 and breast cancer resistance protein and their correlation in breast cancer

WANG Xing¹,JIANG Zhen¹,SUN Chang-gang²

1.Department of Oncology, The People’s Hospital of Yucheng City, Dezhou Shandong 251200, China;
2.Weifang Institute of Traditional Chinese Medicine, Weifang Shandong 261041, China

Published:2014-03-31 Online:2014-04-01
Contact: JIANG Zhen E-mail: dzjiangzhen@163.com

摘要/Abstract

摘要：

背景与目的：乳腺癌患者对化疗药物耐药是导致化疗失败的主要原因。有研究证实，肿瘤干细胞标志物乙醛脱氢酶1(aldehyde dehydrogenase 1，ALDH1)与某些抗癌药物(如环磷酰胺、顺铂等)的耐药有关，并发现经这些药物治疗后的患者癌灶细胞中ALDH1的含量较治疗前高。乳腺癌耐药蛋白(breast cancerresistance protein，BCRP)不仅在正常组织中表达，更高表达于治疗后的乳腺癌中，提示这可能与肿瘤耐药机制相关。关于在乳腺癌患者中两者是否存在共表达的研究很少，本研究主要探讨ALDH1、BCRP与临床病理特征的关系及两种蛋白表达之间的相关性。方法：采用免疫组化法检测乳腺浸润性导管癌组织石蜡切片中ALDH1与BCRP的表达，研究并探讨它们与临床病理特征的关系以及两者表达之间是否有相关性。结果：ALDH1、BCRP在乳腺癌及癌旁乳腺组织中表达差异有统计学意义(χ²=14.685，P=0.000；χ²=12.243，P=0.000)。ALDH1的表达与患者年龄、病理分期、腋窝淋巴结转移、组织学分级及雌激素受体(estrogen receptor，ER)、孕激素受体(progesterone receptor，PR)、人类表皮生长因子受体(human epidermal growth factor receptor，HER-2)状态均无关(P>0.05)；BCRP的表达与HER-2高表达有关，HER-2高表达组的癌组织中BCRP阳性表达率较高，差异有统计学意义(χ²＝5.289，P＝0.021)。BCRP的表达与患者年龄、肿瘤分化程度、腋窝淋巴结转移、病理分期及ER、PR状态无关(P>0.05)；乳腺癌肿瘤干细胞标志物ALDH1与BCRP无相关性(r=-0.039，P=0.786)。结论：ALDH1可能是区别于其他耐药蛋白的一种独立的生物学因子，参与乳腺癌的化疗耐药或肿瘤的侵袭、转移等恶性生物学行为。

关键词: 乳腺浸润性导管癌, 肿瘤干细胞, 乙醛脱氢酶1, 乳腺癌耐药蛋白, 免疫组织化学

Abstract:

Background and purpose: Resistance to antitumor agents is a major cause of treatment failure in patients with breast cancer. Research has shown that, tumor stem cell marker aldehyde dehydrogenase 1 (ALDH1) is related with some anticancer drugs (such as cyclophosphamide, cisplatin) resistance, and the content of ALDH1 in tumor cells after treatment is higher than that before treatment. Breast cancer resistance protein (BCRP) is not expressed in normal tissues, but high expressed in breast cancer of after treatment, it may be associated with the mechanism of tumor drug resistance. This study was to investigate the correlation between expression and the relationship between these two kinds of protein ALDH1, BCRP and clinical pathological characteristics. Methods: Immunohistochemistry was performed to detect the expression of ALDH1 and BCRP in breast infiltrating ductal carcinoma tissues, and whether there is a correlation between and explore their relationship with clinical pathological features and their expression. Results: The expression of ALDH1 protein and BCRP protein in breast cancer and paracarcinoma breast tissues has significant difference(χ²=14.685, P=0.000; χ²=12.243, P=0.000).The expression of ALDH1 with patients age, pathologic stage, axillary lymph node metastasis, histological grading, ER, PR, and HER-2 state were not relevant(P>0.05). HER-2, BCRP protein, expression was higher in cancer tissue (χ²=5.289, P=0.021). There were no relevant with the expression of BCRP with patients age, pathologic stage, axillary lymph node metastasis and histological grading, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor (HER-2) (P>0.05). Conclusion: ALDH1 proteins may be an independent factor compared with occur drug resistant protein, and participate breast cancer drug resistance in the chemotherapy and tumor invasion and metastasis of malignant biological behavior.

Key words: Breast infiltrating ductal carcinoma, Breast cancer resistance protein, Aldehyde dehydrogenase 1, Immunohistochemistry

王兴,姜真,孙长岗. 乙醛脱氢酶1与乳腺癌耐药蛋白在乳腺癌中的表达及相关性研究[J]. 中国癌症杂志, 2014, 24(3): 175-181.

WANG Xing,JIANG Zhen,SUN Chang-gang. Research of expression of aldehyde dehydrogenase 1 and breast cancer resistance protein and their correlation in breast cancer[J]. China Oncology, 2014, 24(3): 175-181.

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乙醛脱氢酶1与乳腺癌耐药蛋白在乳腺癌中的表达及相关性研究

Research of expression of aldehyde dehydrogenase 1 and breast cancer resistance protein and their correlation in breast cancer

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