Molecular analysis of etiological factors and malignant degrees for non-small cell lung cancer

非小细胞肺癌病因及恶性程度的分子分析

• 批准号: 15590327
• 负责人: TSUCHIYA Eiju
• 金额: $ 2.11万
• 依托单位: Kanagawa Cancer Center Research Institute (2004-2005)Research Institute for Clinical Oncology, Saitama Cancer Center (2003)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590327/
• 关键词: Lung cancer; non-small cell carcinoma; Squamous cell carcinoma; Adenocarcinoma; malignancy; Carcinogenesis; p53; k-ras; 扁平上皮癌; K-ras; 非小細胞肺がん; p53遺伝子; マイクロダイセクション; 非小細胞癌

74 resected squamous cell carcinomas (sqs) and 239 adenocarcinomas were analyzed for p53 mutation : Any relationships between tumor location of sqs or subtype of adenocarcinomas, smoking, and p53 mutation patterns were then examined focusing on varying etiological factors. Our hypothesis was, that G→T transversion of p53 gene is caused by direct action of carcinogens contained in tobacco smoke on DNA, and that G→A transition at CpG (CpG→A) sites of the gene is caused by endogenous mechanisms. The same adenocarcinoma cases were also analyzed to determine what type of combined mutation status on p53 and k-ras affects malignancy of the tumors more strongly.Results:1) Sqs were divided into three types by location - central, intermediate and periphera l; the highest frequencies of CpG→A in the central type, G→T in the intermediate and other mutations in the peripheral, were observed. 2)Adenocarcinomas were divided into five types - hobnail, columnar, goblet, polygonal and mixed. Of these, the hobnail type showed a low p53 mutation frequency with the highest CpG→A rate, the columnar and polygonal types had a high mutation frequency with the highest G→T rates, and the mixed type showed intermediate frequency of p53 with the highest other base change. 3)Five year survival was the highest for adenocarcinomas with the combination of non-mutated p53 and k-ras, followed by the combination of mutated p53 and non-mutated k-ras, and then the combination of non-mutated p53 and mutated k-ras, with the combination of mutated p53 and k-ras having the lowest survival.The results show that etiological factors vary depending on locations of sqs and subtype of adenocarcinomas ; the worst malignancy was adenocarcinomas with the combined status on mutated p53 and k-ras.

对74例鳞状细胞癌(SQS)和239例腺癌进行了p53突变分析：然后重点研究了不同的病因，分析了SQS的肿瘤位置与腺癌亚型、吸烟和p53突变模式之间的关系。我们的假设是，P53基因的G-→T颠倒是由烟草烟雾中含有的致癌物直接作用于脱氧核糖核酸引起的，而该基因CpG(CpG-→A)位点的G-→A转换是由内源性机制引起的。结果：1)鳞癌按部位分为中央型、中间型和周围型L，中央型、中间型和周围型突变频率最高，中间型和外周型突变频率最高。2)腺癌分为鞋钉型、柱状型、杯状型、多角型和混合型。其中，鞋钉型突变率低，CpG→A率最高，柱状型和多边形型突变率高，G→T率最高，混合型突变率中等，其他碱基改变最高。3)非突变P53和k-ras联合表达的腺癌5年生存率最高，其次是突变P53和非突变k-ras联合表达，其次是非突变P53和突变k-ras结合表达，而突变P53和k-ras结合表达的腺癌5年生存率最低。

项目成果

Molecular markers for reinforcement of histological subclassification of neuroendocrine lung tumors

• DOI: 10.1111/j.1349-7006.2004.tb03212.x
• 发表时间: 2004-04
• 期刊: Cancer Science
• 影响因子: 5.7
• 作者: Yasuhito Kobayashi;Y. Tokuchi;T. Hashimoto;M. Hayashi;H. Nishimura;Y. Ishikawa;K. Nakagawa;Y. Sato;Atsushi Takahashi;E. Tsuchiya

p53 mutation spectra for squamous cell carcinomas at different levels of human bronchial branches

• DOI: 10.1002/ijc.21877
• 发表时间: 2006-08
• 期刊: International Journal of Cancer
• 影响因子: 6.4
• 作者: Takuo Shimmyo;T. Hashimoto;Yasuhito Kobayashi;Y. Miyagi;Y. Ishikawa;K. Nakagawa;H. Osada;E. Tsuchiya

肺癌、病理診断に役立つ分子病理学・10、シリーズ最新医学講座・II.

对肺癌病理诊断有用的分子病理学/10，最新医学课程系列/II．

• 发表时间: 2004
• 期刊: 臨床検査 48
• 作者: 石川雄一;土屋永寿
• 通讯作者: 土屋永寿

ADAM8 as a novel serological and histochemical marker for lung cancer

• DOI: 10.1158/1078-0432.ccr-04-1436
• 发表时间: 2004-12-15
• 期刊: CLINICAL CANCER RESEARCH
• 影响因子: 11.5
• 作者: Ishikawa, N;Daigo, Y;Nakamura, Y
• 通讯作者: Nakamura, Y

Kobayashi K, Tokuchi Y, Hashimoto T.M Tsuchiva E.et al.: "Molecular markers for reinforcement of histological subclassification of neuroendocrine lung tumors"Cancer Science. (in press).

Kobayashi K、Tokuchi Y、Hashimoto T.M Tsuchiva E.等人：“用于强化神经内分泌肺肿瘤组织学亚分类的分子标记”癌症科学。