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

肺腺癌的预后非常差。 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,绒毛膜癌，畸胎瘤，肝细胞癌和Wilm的肿瘤。从2005年和2006年，从东京大学医院病理学系的文件中检索了肺组织标本。可以通过EGFR突变和GPC3免疫染色来分析32个样品。在11例32例（34％）中检测到EGFR突变。 GPC3在8例中为阳性，包括6例具有混合亚型的腺癌，一种粘蛋白产生的固体腺癌和分化良好的胎儿腺癌。在两种情况下，GPC3周的表达和EGFR突变都被检测到更多的离子。基因表达谱揭示了GPC3在18个肺腺癌细胞系之一中的表达。这些结果表明，在肺腺癌中的GPC3表达广泛表明胎儿型腺癌和GPC3被许诺被靶向分子靶向药物的候选者。2在人类肺腺癌中，最近重要的话题是EGFR Kinase抑制剂，GEFFR KINASE抑制剂，Gefiters，Gefitibib和Erlotinib，Erlotinib和Erlotib erlotib。替代本构主动信号分子的候选者之一是C-MET，而不是EGFR途径。在12个肺腺癌细胞系中检测到C-MET的组成型激活。 C-MET过表达的机制是，无论是否有或没有基因扩增，配体独立于配体并取决于细胞矩阵粘合剂。3肿瘤缺氧与癌细胞的恶性表型和较差的患者及时有关。在A549肺腺癌细胞系中，缺氧诱导细胞运动性，EGFR基因表达水平EGFR抑制剂AG1478完全抑制了通过缺氧诱导的细胞运动。较少的