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Molecular and Clinical database and Molecular Staging for Lung Cancer

肺癌分子和临床数据库以及分子分期

基本信息

批准号：
16591424
负责人：
MITSUDOMI Tetsuya
金额：
$ 2.3万
依托单位：
Aichi Cancer Center Research Institute
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16591424/
关键词：
lung cancer EGFR K-ras p53 prognostic factor predictive factor number of metastatic lymph nodes database PIK3CA PTEN 上皮成長因子受容体(EGFR)腺癌 K-ras遺伝子 p53遺伝子非喫煙者肺癌

项目摘要

Just after the initiation of this project, mutations of the gene for epidermal growth factor receptor (EGFR) were discovered. Accordingly, our main efforts were made on mutational analyses of the EGFR, K-ras, p53 and PIKsCA gene and their clinical implications.EGFR were present in 111 (40%) in 277 lung cancer cases. Exon 19 deletion (47%) and point mutation at codon 858 in exon 21 (44%) accounted for more than 90% of the mutations. EGFR mutations were siginificantly more frequent in women than men, in non-smokers than ever-smokers, and in adenocarcinoma than non-adenocarcinoma (all P<0.001). EGFR mutations and K-ras mutations had mutually exclusionary relationship, however, p53 mutations occurred independently of the EGFR mutations.In 59 patients who received gefitinib for their recurrent disease, EGFR mutations were present in 33. Response to gefitinib was observed in 83% of the patients with EGFR mutations and in 10 of those without EGFR mutation. Patients with EGFR mutations survived for a significantly longer period. In this cohort, K-ras mutations were found in 9 and none of these patients responded to gefitinib. Survival was shorter in this group of patients. Two patients had PIK3CA mutation as well as EGFR mutation.To further develop clinical database, we also evaluated effects of number of metastatic lymph nodes on patient survival. Number of metstatic node proved to be useful predictor of prognosis and may add further information to the current TNM staging system.

就在该项目启动后，发现了表皮生长因子受体（EGFR）基因的突变。因此，我们主要研究了EGFR、K-ras、p53和PIKsCA基因的突变及其临床意义。外显子19缺失（47%）和外显子21第858位密码子点突变（44%）占突变总数的90%以上。EGFR突变在女性中的发生率显著高于男性，在非吸烟者中的发生率显著高于吸烟者，在腺癌中的发生率显著高于非腺癌（均P<0.001）。EGFR突变与K-ras突变存在相互排斥关系，而p53突变与EGFR突变无关。在83%的EGFR突变患者和10例无EGFR突变患者中观察到对吉非替尼的反应。携带EGFR突变的患者存活时间明显更长。在该队列中，9例患者发现K-ras突变，这些患者对吉非替尼无应答。这组患者的生存期较短。2例患者同时存在PIK 3CA突变和EGFR突变，为了进一步建立临床数据库，我们还评估了转移淋巴结数量对患者生存率的影响。转移淋巴结的数目被证明是有用的预后预测因子，并可能为目前的TNM分期系统增加更多的信息。