Identification of new genes associated with breast cancer progression by gene expression analysis of predefined sets of neoplastic tissues
Identification of new genes associated with breast cancer progression by gene expression analysis of predefined sets of neoplastic tissues
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DOI：
10.1002/ijc.23660
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发表时间：
2008-09-15
影响因子：
6.4
通讯作者：
De Bortoli, Michele
中科院分区：
文献类型：
--
作者：
Cimino, Daniela;Fuso, Luca;De Bortoli, Michele
应用微阵列技术研究了两组临床预后不同的乳腺癌患者的基因表达谱。比较术后72个月内30例复发者和30例未复发者，共鉴定出77个差异表达基因。这些基因具有特定的本体分布，其中一些基因在以前的研究中被认为与乳腺癌有关：AIB1，两个角蛋白基因Krt5和KRT15，RAF1，WIF1和MSH6。从127例乳腺癌组织中筛选出77个差异表达基因中的7个进行qRT-PCR分析。6个上调基因(CKMT1B、DDX21、PRKDC、PTPN1、SLPI、YWHAE)的表达水平与无病生存和总体生存密切相关。使用显著因素(即雌激素受体和淋巴结状况)作为协变量的多变量分析证实了与生存的关联。这些基因的表达水平与其他临床参数之间无相关性。相比之下，SERPINA3是唯一被检测到的下调基因，与生存无关，但与类固醇受体状态有关。通过在3个公开可用的微阵列数据集中计算它们与存活率的关联，提供了对我们的基因的间接验证。在所有3个数据集中，CKMTIB的表达是一个独立的预后标记物，而在至少I个数据集中，其他基因证实了它们与无病生存的关联。这项工作提供了一组新的基因，可以用作乳腺癌的独立预后标志和潜在的药物靶点。(C)2008年Wiley-Liss，Inc.
Gene expression profiles were studied by microarray analysis in 2 sets of archival breast cancer tissues from patients with distinct clinical outcome. Seventy-seven differentially expressed genes were identified when comparing 30 cases with relapse and 30 cases without relapse within 72 months from surgery. These genes had a specific ontological distribution and some of then) have been linked to breast cancer in previous studies: AIB1, the two keratin genes KRT5 and KRT15, RAF1, WIF1 and MSH6. Seven out of 77 differentially expressed genes were selected and analyzed by qRT-PCR in 127 cases of breast cancer. The expression levels of 6 upregulated genes (CKMT1B, DDX21, PRKDC, PTPN1, SLPI, YWHAE) showed a significant association to both disease-free and overall survival. Multivariate analysis using the significant factors (i.e., estrogen receptor and lymph node status) as covariates confirmed the association with survival. There was no correlation between the expression level of these genes and other clinical parameters. In contrast, SERPINA3, the only downregulated gene examined, was not associated with survival, but correlated with steroid receptor status. An indirect validation of our genes was provided by calculating their association with survival in 3 publicly available microarray datasets. CKMTIB expression was an independent prognostic marker in all 3 datasets, whereas other genes confirmed their association with disease-free survival in at least I dataset. This work provides a novel set of genes that could be used as independent prognostic markers and potential drug targets for breast cancer. (C) 2008 Wiley-Liss, Inc.