Expression signatures in lung cancer reveal a profile for EGFR-mutant tumours and identify selective PIK3CA overexpression by gene amplification
Expression signatures in lung cancer reveal a profile for EGFR-mutant tumours and identify selective PIK3CA overexpression by gene amplification
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DOI：
10.1002/path.2267
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发表时间：
2008-02-01
影响因子：
7.3
通讯作者：
Sanchez-Cespedes, M.
中科院分区：
文献类型：
--
作者：
Angulo, B.;Suarez-Gauthier, A.;Sanchez-Cespedes, M.
靶向治疗的发展需要通过肿瘤的组织学和遗传学特征准确区分肿瘤。在这里，我们的目标是确定基因表达谱和单一的标志物，概括的病理和遗传背景的非小细胞肺癌（NSCLC）。我们对一系列69例非小细胞肺癌（NSCLC）和6例正常肺组织进行了cDNA微阵列分析，这些NSCLC具有已知的重要基因突变状态。无监督聚类分析根据其组织病理学和EGFR突变的存在将正常肺与肺肿瘤和肺肿瘤分离。相对于腺癌（AC），鳞状细胞癌（SCC）中的几种转录物高度过表达（接近20倍），并在75个肺肿瘤的独立队列中通过免疫组化证实。13个基因的表达构成了EGFR突变肿瘤最突出的标志，包括脯氨酸脱氢酶（PRODH）水平的增加和X盒结合蛋白1（XBP 1）的下调。没有基因差异表达，倍数变化>= 4或
The development of targeted therapies creates a need to discriminate tumours accurately by their histological and genetic characteristics. Here, we aim to identify gene expression profiles and single markers that recapitulate the pathological and genetic background of non-small cell lung cancer (NSCLC). We performed cDNA microarray analysis on a series of 69 NSCLCs, with known mutation status for important genes, and six normal lung tissues. Unsupervised cluster analysis segregated normal lungs from lung tumours and lung tumours according to their histopathology and the presence of EGFR mutations. Several transcripts were highly overexpressed (by similar to 20 times) in squamous cell carcinomas (SCCs) relative to adenocarcinomas (ACs) and confirmed by immunohistochemistry in an independent cohort of 75 lung tumours. Expression of 13 genes constituted the most prominent hallmarks of EGFR-mutant tumours, including increased levels of proline dehydrogenase (PRODH) and down-regulation of X-box binding protein 1 (XBP1). No genes were differentially expressed, with a fold change >= 4 or