MUC1-induced transcriptional programs associated with tumorigenesis predict outcome in breast and lung cancer.
MUC1-induced transcriptional programs associated with tumorigenesis predict outcome in breast and lung cancer.
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DOI：
10.1158/0008-5472.can-08-4513
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发表时间：
2009-04-01
期刊：
影响因子：
11.2
通讯作者：
Weichselbaum RR
中科院分区：
文献类型：
--
作者：
Khodarev NN;Pitroda SP;Beckett MA;MacDermed DM;Huang L;Kufe DW;Weichselbaum RR
粘蛋白1（MUC1）癌蛋白在包括乳腺癌和肺癌在内的多种人类恶性肿瘤中异常过表达。虽然MUC1调节几种转录因子的活性，但没有关于MUC1对全局基因表达模式的影响以及MUC1诱导的基因在预测癌症患者预后中的潜在作用的信息。我们已经开发了一种MUC1诱导转化的实验模型，该模型已经确定了参与肿瘤发生、血管生成和细胞外基质重塑的基因家族的激活。一组实验衍生的MUC1诱导的基因与肿瘤发生的乳腺癌和肺腺癌癌症数据库的分析。35个基因MUC1诱导的肿瘤发生特征预测乳腺癌（n = 295）和肺癌（n = 442）患者的无病生存期和总生存期均显著降低。这些数据表明，MUC1癌蛋白有助于调节对乳腺癌和肺癌患者的临床结果具有高度预测性的基因。
The Mucin 1 (MUC1) oncoprotein is aberrantly overexpressed in diverse human malignancies including breast and lung cancer. Although MUC1 modulates the activity of several transcription factors, there is no information regarding the effects of MUC1 on global gene expression patterns and the potential role of MUC1-induced genes in predicting outcome for cancer patients. We have developed an experimental model of MUC1-induced transformation that has identified the activation of gene families involved in oncogenesis, angiogenesis, and extracellular matrix remodeling. A set of experimentally derived MUC1-induced genes associated with tumorigenesis was applied to the analysis of breast and lung adenocarcinoma cancer databases. A 35-gene MUC1-induced tumorigenesis signature predicts significant decreases in both disease-free and overall survival in patients with breast (n = 295) and lung (n = 442) cancers. The data show that the MUC1 oncoprotein contributes to the regulation of genes that are highly predictive of clinical outcome in breast and lung cancer patients.