Analysis of integrin β4 expression in human breast cancer:: Association with basal-like tumors and prognostic significance
Analysis of integrin β4 expression in human breast cancer:: Association with basal-like tumors and prognostic significance
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DOI：
10.1158/1078-0432.ccr-07-4116
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发表时间：
2008-02-15
影响因子：
11.5
通讯作者：
Mercurio, Arthur M.
中科院分区：
文献类型：
--
作者：
Lu, Shaolei;Sirnin, Karl;Mercurio, Arthur M.
目的：基于从细胞系和小鼠模型获得的数据，β 4整联蛋白已经涉及与癌的发生和进展相关的功能。然而，关于其表达和与人类癌症相关性的数据相对较少。本研究的目的是评估其表达和预后意义在人类breast carcinoma.Experimental设计：我们整合了数据从多个基因分析研究乳腺肿瘤的已知临床结果与免疫组化分析105乳腺癌，我们确定了基因的表达相关的β 4。β 4 mRNA和蛋白在乳腺癌中的表达是不均匀的，它与乳腺癌的“基底样”亚型最显著相关（P = 0.008）。4和HER2表达之间没有明显的关联，无论是基因分析或免疫组化分析。为了深入了解β 4表达与人类乳腺癌的相关性，我们基于四项已发表的基因谱研究的整合生成了65个基因的“β 4签名”，其中包括与β 4正相关或负相关的前0.1%的基因。当应用于包括两个独立的数据集的四个数据集时，β 4特征预测了肿瘤复发和患者生存时间的减少。这些观察结果表明，β 4在人乳腺癌中的表达是有限的，并与基底样癌相关，他们支持这样的假设，即β 4可能与一组离散的蛋白质协同作用，以促进一个子集的攻击行为。肿瘤的
Purpose: The beta 4 integrin has been implicated in functions associated with the genesis and progression of carcinomas based on data obtained from cell lines and mouse models. Data on its expression and relevance to human carcinomas, however, are relatively scant. The aim of this study was to assess its expression and prognostic significance in human breast carcinomas.Experimental Design: We integrated data on beta 4 expression from multiple gene profiling studies of breast tumors of known clinical outcome with immunohistochemical analysis of 105 breast carcinomas, and we identified genes whose expression correlates with that of beta 4.Results: The expression of both beta 4 mRNA and protein is not homogeneous in breast cancer and it associates most significantly with the "basal-like" subtype of breast tumors (P = 0.008). No association between 4 and HER2 expression was evident from either gene profiling or immunohistochemical analysis. To gain insight into the relevance of 4 expression to human breast carcinomas, we generated a 65-gene "beta 4 signature" based on integration of four published gene profiling studies that included the top 0.1% of genes that correlated with beta 4, either positively or negatively. This beta 4 signature predicted decreased time to tumor recurrence and survival of patients when applied to four data sets including two independent ones.Conclusions: These observations indicate that beta 4 expression in human breast cancer is restricted and associated with basal-like cancers, and they support the hypothesis that beta 4 may function in concert with a discrete set of proteins to facilitate the aggressive behavior of a subset of tumors.