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中华乳腺病杂志(电子版)

中华乳腺病杂志(电子版) ›› 2018, Vol. 12 ›› Issue (05) : 270 -275. doi: 10.3877/cma.j.issn.1674-0807.2018.05.003

所属专题： 文献；

论著

乳腺癌患者外周血中内皮祖细胞检测的临床意义
王佳铭1, 魏刚1,†(), 马震2, 王长青1, 严时3, 刘岩3, 李慧3   
  1. 1. 130012　长春，吉林省肿瘤医院乳腺肿瘤外科
    2. 130012　长春，吉林省人民医院乳腺科
    3. 130012　长春，吉林省肿瘤医院肿瘤转化医学实验室
  • 收稿日期:2016-09-07 出版日期:2018-10-01
  • 通信作者: 魏刚
  • 基金资助:
    吉林省卫生厅课题(2017J027，2015Z095); 吉林省科技厅课题(20140101170JC)

Determination of endothelial progenitor cells in peripheral blood of breast cancer patients

Jiaming Wang1, Gang Wei1,†(), Zhen Ma2, Changqing Wang1, Shi Yan3, Yan Liu3, Hui Li3   

  1. 1. Department of Breast Oncologic Surgery, Jilin Cancer Hospital, Changchun 130012, China
    2. Department of Breast Diseases, People’s Hospital of Jilin Province, Changchun 130012, China
    3. Translational Research Laboratory of Oncology, Jilin Cancer Hospital, Changchun 130012, China
  • Received:2016-09-07 Published:2018-10-01
  • Corresponding author: Gang Wei
  • About author:
    Corresponding author: Wei Gang, Email:
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王佳铭, 魏刚, 马震, 王长青, 严时, 刘岩, 李慧. 乳腺癌患者外周血中内皮祖细胞检测的临床意义[J]. 中华乳腺病杂志(电子版), 2018, 12(05): 270-275.

Jiaming Wang, Gang Wei, Zhen Ma, Changqing Wang, Shi Yan, Yan Liu, Hui Li. Determination of endothelial progenitor cells in peripheral blood of breast cancer patients[J]. Chinese Journal of Breast Disease(Electronic Edition), 2018, 12(05): 270-275.

目的

探讨乳腺癌患者外周血中内皮祖细胞(EPCs)检测的临床意义。

方法

采用前瞻性研究方法，收集2014年3月至2015年3月吉林省肿瘤医院收治的、病理学证实的70例浸润性乳腺导管癌患者、61例乳腺纤维腺瘤患者和68名健康人的外周血，利用流式细胞术检测EPCs[CD34、CD133和血管内皮生长因子受体(VEGFR)-2阳性细胞]水平。采用Fisher确切概率检验和Kruskal-Wallis H检验比较3组间EPCs阳性率及其表面标志物CD34、CD133和VEGFR-2表达量的差异，并用Fisher确切概率检验分析乳腺癌患者EPCs阳性率与临床病理特征的关系；采用t检验比较不同临床分期和不同淋巴结转移状态患者间EPCs表面标志物CD34、CD133和VEGFR-2表达量的差异。

结果

在乳腺癌患者、乳腺纤维腺瘤患者和健康人外周血中，EPCs阳性率及其表面标志物CD34、CD133和VEGFR-2表达量的差异均有统计学意义(χ2＝12.811，P<0.001；F＝15.275，P<0.001)；健康人及乳腺纤维腺瘤组均未检测到EPCs，组间两两比较显示，EPCs表面标志物CD34、CD133和VEGFR-2在乳腺癌患者外周血中的表达量[M(P25～P75)：0.006%(0.003%～6.008%)]明显高于健康人及乳腺纤维腺瘤患者(P＝0.002、0.003)，乳腺癌组EPCs阳性率也显著高于健康人及乳腺纤维腺瘤患者[11.4%(8/70)分别比0(0/68)、0(0/61)，P＝0.006、0.007]。但EPCs阳性率与乳腺癌患者的年龄、ER、PR和HER-2状态均无关(P均>0.050)。进一步分析EPCs阳性的8例乳腺癌患者临床资料后发现，Ⅰ期患者(n＝4)外周血中EPCs表面标志物CD34、CD133和VEGFR-2的表达量明显低于Ⅱ～Ⅳ期患者(n＝4)[(0.300±0.162)%比(1.130±0.318)%，t＝4.640，P＝0.004]，而淋巴结转移者(n＝4)EPCs表面标志物CD34、CD133和VEGFR-2的表达量明显高于未转移者(n＝4)[(1.062±0.424)%比(0.370±0.287)%，t＝2.700，P＝0.040]。

结论

乳腺癌患者外周血中EPCs表面标志CD34、CD133和VEGFR-2表达水平较高，其可能是一种潜在的生物标志物和治疗靶点。

关键词: 乳腺肿瘤, 内皮，血管, 血管内皮生长因子受体2, 抗原，CD, 内皮祖细胞
Objective

To investigate the clinical significance of endothelial progenitor cells (EPCs) in peripheral blood of breast cancer patients.

Methods

Peripheral blood from healthy volunteers (control group, n=68), breast fibroadenoma patients (benign group, n=61) and patients with invasive ductal breast cancer (n=70) in Jilin Cancer Hospital from March 2014 to March 2015 were collected for a prospective study. The concentration of EPCs (marked by CD34, CD133 and VEGFR-2 positive) was determined by flow cytometry. Fisher’s exact probability test and Kruskal-Wallis H test were used to compare the positive rate of EPCs and the expression of CD34, CD133 and VEGFR-2 among three groups. Fisher’s exact probability test was used to analyze the relationship between the positive rate of EPCs and clinicopathological features in breast cancer patients. The expression of CD34, CD133 and VEGFR-2 (surface markers of EPCs) was compared in the patients with different clinical stages and lymph node metastasis status by t test.

Results

The positive rate of EPCs and the expression of CD34, CD133 and VEGFR-2 presented a significant difference among three groups (χ2=12.811, P<0.001; F=15.275, P<0.001). EPCs were not detected in control group and benign group. The expression of CD34, CD133 and VEGFR-2 in breast cancer group was 0.006%(0.003%-0.008%)[M(P25-P75)], significantly higher than that in control group or benign group (P=0.002 and P=0.003). The positive rate of EPCs was significantly higher than that in control group or benign group [11.4% (8/70) vs 0 (0/68), P=0.006; 11.4% (8/70) vs 0 (0/61), P=0.007]. The positive rate of EPCs was not correlated with patient age, ER, PR and HER-2 status (all P>0.05). In eight breast cancer patients with EPCs positive, the expression of CD34, CD133 and VEGFR-2 in stageⅠbreast cancer was significantly lower than that in stage Ⅱ-Ⅳ breast cancer [(0.300±0.162)% vs (1.130±0.318)%, t=4.640, P=0.004), and the expression of CD34, CD133 and VEGFR-2 in patients with lymph node metastasis was significantly higher than that in patients without [(1.062±0.424)% vs (0.370±0.287)%, t=2.700, P=0.040].

Conclusion

CD34, CD133 and VEGFR-2(surface markers of EPCs) have high expression in peripheral blood of breast cancer patients, so EPCs might serve as a potential biomarker and a therapeutic target.

Key words: Breast neoplasms, Endothelium, blood vessels, Endothelial growth factor receptor-2, Antigens, CD, Endothelial progenitor cells
图1 流式细胞术检测脐带血中单个核细胞群的分布情况　a图所示脐带血中单个核细胞群；b图所示单个核细胞群中的CD45＋细胞(白细胞)
图2 流式细胞术检测脐带血中EPCs分布情况　a和b图分别为CD309 PE和CD133 APC同型阴性对照抗体表达图；c图为脐带血单核细胞群中CD34和CD309的表达；d图为脐带血单核细胞群中CD133在R3门内细胞中的表达
图3 乳腺癌患者、乳腺纤维腺瘤患者及健康人外周血中EPCs表面标志物CD34、CD133、VEGFR-2(CD309)的表达　a、b、c图，d、e、f图以及g、h、i图分别为健康人、乳腺纤维腺瘤患者和乳腺癌患者外周血中EPCs细胞表面标志物CD34、VEGFR-2和CD133的表达
表1 乳腺癌患者EPCs阳性率与临床病理特征的关系
临床病理特征 例数 EPCs阳性[例(%)] 检验值 P值
年龄 ? ? ? ?
? <50岁 23 2(8.7) ? 1.000a
? ≥50岁 47 6(12.8) ? ?
淋巴结转移 ? ? ? ?
? 有 46 5(10.9) ? 1.000a
? 无 24 3(12.5) ? ?
ER ? ? ? ?
? 阳性 46 6(13.0) ? 0.760a
? 阴性 24 2(8.3) ? ?
PR ? ? ? ?
? 阳性 48 7(14.6) ? 0.420a
? 阴性 22 1(4.5) ? ?
HER-2 ? ? ? ?
? 阳性 23 2(8.7) ? 1.000a
? 阴性 47 6(12.8) ? ?
临床分期 ? ? ? ?
? Ⅰ 23 4(17.4) ? ?
? Ⅱ 21 2(9.5) χ2＝1.121 0.806a
? Ⅲ 12 1(8.3) ? ?
? Ⅳ 14 1(7.1) ? ?
表2 8例EPCs表面标志物CD34、CD133和VEGFR-2阳性表达的乳腺癌患者临床病理特征
临床病理特征 例数 CD34、CD133、VEGFR-2表达量(%) t值 P值
疾病分期 ? ? ? ?
? Ⅰ期 4 0.300±0.162 4.640 0.004
? Ⅱ～Ⅳ期 4 1.130±0.318 ? ?
淋巴结转移 ? ? ? ?
? 是 4 1.062±0.424 2.700 0.040
? 否 4 0.370±0.287 ? ?
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