应用组织芯片进行乳腺癌分子分型的研究
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陈俊强 E-mail:gxhans@163.com

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广西自然科学基金资助项目(桂科自0447058)。


Molecular subtype of breast cancer using tissue chip
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    摘要:

    目的:探索一种能准确地预测乳腺癌预后的分子分型系统。
    方法:筛选70例乳腺癌标本,35例为诊断乳腺癌后5年内死亡者,另35例为存活超过10年者。两组在诊断和治疗等方面均相匹配。采用基于组织芯片的免疫组化技术检测两组标本中17个分子标志物的表达,采用聚类分析对17个标志物进行分组,对分组结果进行生存分析及临床病理参数相关分析。
    结果:17个标志物分为4个亚组:ERα相关组,增殖相关组,PR相关组和HER-2相关组,中位生存时间分别为142,126,88,77个月,差异均有显著性(P=0.044)。Cox模型分析4个亚组的生存时间,相邻两组间死亡风险平均增加了1.623倍。4个亚组与癌肿长径具有低度正相关(Cramer列联系数为0.377)。
    结论:由ERα相关组,PR相关组,增殖相关组和HER-2相关组构成新的乳腺癌分子分型,可以准确地预测乳腺癌患者死亡风险,可作为乳腺癌预测预后的一种新分型方法。

    Abstract:

    Objective:To explore a molecular subtype system for accurately predict the prognosis of breast cancer.
    Methods:Seventy cases of invasive breast cancer were divided into a groups: (1) Group A, 35 cases. These patients died within five years after diagnosis; (2) Group B, 35 cases. These patients were still alive 10 years after diagnosis. The two groups was matched at fields of ages, diagnosis, therapeutic regimens and so on. Immunohistochemistry based on tissue chip was used to detect the expression of 17 molecular biomarkers; hierarchical clustering algorithm was applied to cluster the 17 molecular biomarkers into several subgroups, and survival and clinicopathologic parameters were analyzed and compared in different subgroups.
    Results:Seventeen molecular biomarkers were clustered into four subgroups:ERα related subgroup, PR related subgroup, proliferation related subgroup and HER-2 related subgroup. There was a significant difference in median survival time among the four subgroups: Median survival time of ERα related subgroup, PR related subgroup, proliferation related subgroup and HER-2 related subgroup was 142, 126, 88 and 77months, respectively, (P=0.044). In a multivariate Cox model, the average death risk between the consecutive subgroups increased 1.623 folds. There were low positive correlations in tumor long diameter among four subgroups (Cramer Coefficient of Contingency was 0.377).
    Conclusions:A  new molecular subtype of breast cancer has been found by using immunohistochemistry based on tissue chip and hierarchical clustering algorithm. Molecular subtype of ERα related subgroup, PR related subgroup, proliferation-related subgroup and HER-2 related subgroup can predict patient′s death risk accurately, and could be as a new molecular classification for predicting the prognosis in breast cancer patients.

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陈俊强| 罗善山| 刘金禄| 林进令| 曾健| 陈军.应用组织芯片进行乳腺癌分子分型的研究[J].中国普通外科杂志,2010,19(11):1211-1214.
DOI:10.7659/j. issn.1005-6947.2010.11.013

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  • 收稿日期:2010-03-29
  • 最后修改日期:2010-10-12
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  • 在线发布日期: 2010-11-15