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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.基于凝胶的蛋白质组学(1)与肺癌组织病理学类型相关的蛋白质分析：利用二维聚丙烯酰胺凝胶电泳(2DE)和质谱(MS)鉴定了47种蛋白质(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谱进行分类的可能性以及治疗策略的选择。(2)CDDP耐药相关蛋白分析：在2DE凝胶上鉴定GST-π和reticulocalbin(RCN)斑点，并提出术后选择铂类化疗反应者的可能性。此外，我们使用Ettan DIGE系统检测到107个蛋白过度表达超过1.5倍，120个蛋白表达减少不到0.75倍。(3)我们检测到40和33个蛋白的表达水平被两种酪氨酸激酶抑制剂改变。通过MS对这些蛋白分子进行了鉴定，接下来我们正在进行验证分析。2.利用液相色谱-MS(LC-MS)进行蛋白质组学分析(1)肺腺癌中淋巴结受累相关蛋白的分析：我们比较了t2无病例和t1n(+)病例之间的蛋白表达谱。我们检测到 604 个与淋巴结受累相关的候选蛋白。 (2)肺腺癌早期检测生物标志物的探索：对IA期和III期腺癌患者的血清进行分析，检测到30个候选早期检测生物标志物。我们使用已经建立的检测系统验证了七种候选蛋白质。腺癌患者血清中某些候选蛋白的值升高，但腺癌患者和健康供者血清之间没有统计学上的显着差异。因此，我们没有认识到生物标志物对于早期检测的有用性。基于蛋白质组图谱的分类很可能反映了癌细胞的生物学特征。我们计划对肺癌患者个体化治疗的随访和治疗策略进行进一步的调查和评估。较少的