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Clinicopathological analysis of lung adenocarcinomas by EGFR gene mutation and gene expression analysis

肺腺癌EGFR基因突变及基因表达分析的临床病理分析

基本信息

批准号：
18590321
负责人：
OTA Satoshi
金额：
$ 2.53万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18590321/
关键词：
lung cancer EGFR gene mutation oncofetal protein GPC3 腫瘍

项目摘要

Prognosis of lung adenocarcinomas is extremely poor. This project purpose is that the identification of the candidate molecules for molecularly-targeted drug by gene expression profile and immunohistochemical analyses.1 Analyses of EGFR mutation and oncofetal protein GPC3 expression in lung adenocarcinomas: Recent studies including our reports have shown the expression of oncofetal protein GPC3 in neoplastic cells of Yolk sac tumor, choriocarcinoma, teratoma, hepatocellular carcinoma, and Wilm's tumor. Lung tissue specimens were retrieved from the file of the Department of Pathology, Tokyo University Hospital in 2005 and 2006. The 32 samples could be analyzed both with EGFR mutation and GPC3 immunostaining. EGFR mutation was detected in 11 cases of 32 cases (34%). GPC3 was positive in 8 cases, including 6 adenocarcinomas with mixed subtypes, one solid adenocarcinoma with mucin production, and well differentiated fetal adenocarcinoma. In 2 cases, both week GPC3 expression and EGFR mutat … More ion were detected. Gene expression profile revealed the expression of GPC3 in the one of 18 lung adenocarcinomas cell lines. Those results suggested the GPC3 expression in lung adenocarcinomas broadly indicated the fetal type adenocarcinomas and GPC3 is promising candidate for molecularly-targeted drug.2 In human lung adenocarcinomas, recent important topic was the acquired resistance the EGFR kinase inhibitors, gefitinib and erlotinib. One of the candidates for alternative constitutive active signaling molecule is c-met, instead of EGFR pathway. Constitutive activation of c-Met was detected 5 out of 12 lung adenocarcinomas cell lines. The mechanisms c-Met overexpression were that either with or without gene amplification, ligand-independent and depends on cell-matrix adhesion.3 Tumor hypoxia is associated with a malignant phenotype of cancer cells and poor patient prognosis. In the A549 lung adenocarcinomas cell line, hypoxia induced the cell motility and EGFR gene expression level EGFR inhibitor AG1478 completely inhibited the promotion of cell motility induced by hypoxia. Less

肺腺癌预后极差。本项目目的是通过基因表达谱和免疫组织化学分析鉴定分子靶向药物候选分子肺腺癌中EGFR突变和癌胎蛋白GPC3表达的分析：最近的研究包括我们的报告显示，癌胎蛋白GPC3在卵黄囊瘤、绒毛膜癌、畸胎瘤、肝细胞癌和Wilm肿瘤的肿瘤细胞中表达。肺组织标本取自东京大学医院病理科2005年和2006年的档案。32份样本均可进行EGFR突变和GPC3免疫染色分析。32例患者中检出EGFR突变11例（34%）。GPC3阳性8例，其中混合亚型腺癌6例，产生粘蛋白的实体腺癌1例，分化良好的胎儿腺癌1例。2例患者外周血GPC3表达和EGFR均发生突变。基因表达谱显示GPC3在18株肺腺癌细胞株中的表达。这些结果提示GPC3在肺腺癌中的表达广泛提示胎儿型腺癌，GPC3是分子靶向药物的理想候选物在人肺腺癌中，最近的重要课题是对EGFR激酶抑制剂吉非替尼和厄洛替尼的获得性耐药。c-met是替代EGFR途径的备选组成型活性信号分子之一。12株肺腺癌细胞系中有5株检测到c-Met的组成激活。c-Met过表达的机制有基因扩增和不扩增两种，与配体无关，依赖于细胞-基质粘附肿瘤缺氧与癌细胞的恶性表型和患者预后不良有关。在A549肺腺癌细胞系中，缺氧诱导细胞运动和EGFR基因表达水平，EGFR抑制剂AG1478完全抑制缺氧诱导的细胞运动的促进。少