Gene expression signatures differentiate adenocarcinoma of lung and breast origin in effusions
Gene expression signatures differentiate adenocarcinoma of lung and breast origin in effusions
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DOI：
10.1016/j.humpath.2011.06.015
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发表时间：
2012-05-01
期刊：
影响因子：
3.3
通讯作者：
Wang, Tian-Li
中科院分区：
文献类型：
--
作者：
Davidson, Ben;Stavnes, Helene Tuft;Wang, Tian-Li
晚期肺腺癌和乳腺癌通常累及浆膜腔，引起恶性积液。本研究的目的是比较这两种恶性肿瘤转移的全球基因表达模式，以扩大和改善目前可用于其鉴别诊断的生物标志物的诊断面板，以及定义类型特异性生物靶标。使用来自Illumina的HumanRef-8 BeadChip分析7个乳腺癌和4个肺腺癌渗出液的基因表达谱。差异表达的候选基因进行了验证，使用定量实时聚合酶链反应和免疫组化。使用阵列中所有54，675个基因的无监督分层聚类将肺与乳腺癌样本分开。我们确定了289个独特的探针，显着差异表达在2种癌症的2倍以上，使用适度的t统计，其中65和224在乳腺癌和肺腺癌，分别过表达。在乳腺癌中过表达的基因包括TFF 1、TFF 3、FOXA 1、CA 12、PITX 1、RARRES 1、CITED 4、MYC、TFAP 2A、EFHD 1、TOB 1、SPDEF、FRES 1和TH。在肺腺癌中过表达的基因包括TITF 1、SFTPG、MMP 7、EVA 1、GPR 116、HOP、SCGB 3A 2和MET。15个基因的差异表达通过实时定量PCR验证，8个基因产物的差异通过免疫组织化学证实。表达谱区分乳腺癌和肺腺癌，并鉴定在这两种肿瘤类型中差异表达的基因。这些癌症特有的分子特征可能有助于其鉴别诊断，并可能为治疗靶点发现提供分子基础。(C)2012 Elsevier Inc. All rights reserved.
Lung and breast adenocarcinoma at advanced stages commonly involve the serosal cavities, giving rise to malignant effusions. The aim of the present study was to compare the global gene expression patterns of metastases from these 2 malignancies, to expand and improve the diagnostic panel of biomarkers currently available for their differential diagnosis, as well as to define type-specific biological targets. Gene expression profiles of 7 breast and 4 lung adenocarcinoma effusions were analyzed using the HumanRef-8 BeadChip from Illumina. Differentially expressed candidate genes were validated using quantitative real-time polymerase chain reaction and immunohistochemistry. Unsupervised hierarchical clustering using all 54,675 genes in the array separated lung from breast adenocarcinoma samples. We identified 289 unique probes that were significantly differentially expressed in the 2 cancers by greater than 2-fold using moderated t statistics, of which 65 and 224 were overexpressed in breast and lung adenocarcinoma, respectively. Genes overexpressed in breast adenocarcinoma included TFF1, TFF3, FOXA1, CA12, PITX1, RARRES1, CITED4, MYC, TFAP2A, EFHD1, TOB1, SPDEF, FASN, and TH. Genes overexpressed in lung adenocarcinoma included TITF1, SFTPG, MMP7, EVA1, GPR116, HOP, SCGB3A2, and MET. The differential expression of 15 genes was validated by quantitative real-time PCR, and differences in 8 gene products were confirmed by immunohistochemistry. Expression profiling distinguishes breast adenocarcinoma from lung adenocarcinoma and identifies genes that are differentially expressed in these 2 tumor types. The molecular signatures unique to these cancers may facilitate their differential diagnosis and may provide a molecular basis for therapeutic target discovery. (C) 2012 Elsevier Inc. All rights reserved.