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Proteomic analysis of cancer associated proteins in the solid neoplasm -The analysis for individualized therapy for lung cancer-

实体瘤中癌症相关蛋白的蛋白质组学分析-肺癌个体化治疗分析-

基本信息

批准号：
15390423
负责人：
HIRANO Takashi
金额：
$ 5.31万
依托单位：
Tokyo Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
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

项目摘要

1.Gel based proteomics(1)Analysis of proteins associated with histopathological types of lung cancer : 47 proteins (15 adenocarcinoma associated proteins, 16 squamous cell carcinoma associated proteins and 16 neuroendocrine carcinoma associated proteins) were identified using 2 dimensional polyacrylamide gel electrophoresis (2DE) and mass spectrometry (MS). The validation analysis is on going. We suggest the possibility of the classification based on proteomic profiles and the selection of the therapeutic strategy.(2)Analysis of CDDP resistance associated proteins : The spots of GST-π and reticulocalbin (RCN) were identified on 2DE gel, and we proposed the possibility that the responders for platinum based chemotherapy were selected postoperatively. Furthermore, we detected 107 proteins with more than 1.5 fold overexpression and 120 proteins with less than 0.75 fold reduced expression using Ettan DIGE System.(3)We detected 40 and 33 proteins in which the expression levels were changed … More by two kinds of tyrosine kinase inhibitors. These protein molecules were identified by MS, and sequentially we are carrying out the validation analysis.2.Proteomic analysis using Liquid Chromatography-MS (LC-MS)(1)Analysis of lymph node involvement associated proteins in lung adenocarcinoma : We compared protein expression profiles between t2 no cases and t1 n(+) cases. We detected 604 candidate proteins associated with lymph node involvement. The identification and validation are on going.(2)Exploration of the biomarkers for the early detection of lung adenocarcinoma : We analyzed sera of the patients with stage IA and stage III adenocarcinomas, and thirty candidate biomarkers for early detection were detected. We validated seven candidate proteins using already established assay systems. The values of some candidate proteins were elevated in the sera of adenocarcinoma patients, but there are no statistically significant differences between the sera of adenocarcinoma patients and healthy donors. Therefore, we did not recognize the usefulness of the biomarlcers for early detection.There is a high possibility that the classification based on proteomic profile reflects biological characteristics of cancerous cells. We schedule the further investigations and evaluations for the follow-up and therapeutic strategies towards the individualized therapy of lung cancer patients. Less

1.(1)肺癌组织病理类型相关蛋白分析：采用二维聚丙烯酰胺凝胶电泳（2DE）和质谱（MS）技术，共鉴定出47种蛋白（15种腺癌相关蛋白、16种鳞状细胞癌相关蛋白和16种神经内分泌癌相关蛋白）。验证分析正在进行中。我们建议基于蛋白质组学的分类和治疗策略的选择的可能性。(2) CDDP耐药相关蛋白分析：在2DE凝胶上发现GST-π和reticulocalbin （RCN）的斑点，并提出术后选择铂类化疗应答者的可能性。此外，我们使用Ettan DIGE系统检测到107个过表达量超过1.5倍的蛋白和120个表达量低于0.75倍的蛋白。(3)两种酪氨酸激酶抑制剂分别改变了40种和33种蛋白的表达水平。这些蛋白分子经质谱鉴定，并依次进行验证分析。(1)肺腺癌淋巴结累及相关蛋白的分析：我们比较了t2例无病例和t1 n（+）例的蛋白表达谱。我们检测到604种与淋巴结受累相关的候选蛋白。鉴定和验证正在进行中。(2)探索肺腺癌早期检测的生物标志物：我们分析了IA期和III期腺癌患者的血清，检测到30个候选的早期检测生物标志物。我们使用已经建立的分析系统验证了7个候选蛋白。腺癌患者血清中部分候选蛋白值升高，但腺癌患者血清与健康供者血清无统计学差异。因此，我们没有认识到生物标志物对早期检测的有用性。基于蛋白质组学的分类很有可能反映了癌细胞的生物学特性。我们计划对肺癌患者的随访和治疗策略进行进一步的调查和评估。少