The complete family of epidermal growth factor receptors and their ligands are co-ordinately expressed in breast cancer

The complete family of epidermal growth factor receptors and their ligands are co-ordinately expressed in breast cancer
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DOI:
10.1007/s10549-009-0536-5
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发表时间:
2010-07-01
影响因子:
3.8
通讯作者:
Gullick, William J.
Gullick, William J.
中科院分区:
医学2区
文献类型:
--
作者:
McIntyre, Emmet;Blackburn, Edith;Gullick, William J.

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应用免疫组化染色法测定了100例乳腺癌组织中表皮生长因子家族的4种受体和11种配体的表达水平。在某些情况下,所有家庭成员都在某种程度上受到了影响;然而,个别病例显示家庭的表达范围很广,从基本上没有到所有因素都在高水平上。受体的总表达量最高的是HER2,其次是HER1,然后是HER3,最后是HER4。配体(包括NRG1和NRG2基因的两个剪接变体)大致分为三组,其中聚集表达量最高的是Epigen、Epiregulin、Neuregulin 1 α、Neuregulin 2 α、Neuregulin 2 β、Neuregulin 4和TGF α,与EGF、Neuregulin 1 β和Neuregulin 3均有中等表达,HB-EGF、Betacellulin和Amphiregulin表达量相对较低。利用Spearman秩相关进行统计分析,各因子之间的表达呈正相关。使用Cox比例风险模型分析数据显示,在该数据集中,最有效的无复发间隔和总生存期预测因子是仅Epigen和Neuregulin 4的联合测量。
The levels of expression of the four receptors and eleven ligands composing the epidermal growth factor family were measured using immunohistochemical staining in one hundred cases of breast cancer. All of the family were expressed to some degree in some cases; however, individual cases showed a very wide range of expression of the family from essentially none to all the factors at high levels. The highest aggregate level of expression of a receptor was HER2 followed by HER1, then HER3, then HER4. The ligands (including two splice variants of the NRG1 and NRG2 genes) broadly fell into three groups, those with the highest aggregate expression were Epigen, Epiregulin, Neuregulin 1 alpha, Neuregulin 2 alpha, Neuregulin 2 beta, Neuregulin 4 and TGF alpha, moderate expression was seen with EGF, Neuregulin 1 beta and Neuregulin 3, and relatively low levels of expression were seen of HB-EGF, Betacellulin and Amphiregulin. Statistical analysis using Spearman's Rank Correlation showed a positive correlation of expression between each of the factors. Analysing the data using the Cox Proportional Hazards model showed that, in this dataset, the most powerful predictors of relapse free interval and overall survival were the combined measurement of only Epigen and Neuregulin 4.