【摘要】 背景与目的表皮细胞生长因子受体(epidermal growth factor receptor,EGFR)酪氨酸激酶抑制剂(tyrosine kinase inhibitor,TKI)治疗晚期NSCLC患者最终都会出现耐药。本研究目的是检测耐药前后血清蛋白质谱的变化,探索可能用于预测TKI治疗后出现耐药的血清预测因子。方法收集9例晚期NSCLC患者接受吉非替尼(gefitinib)治疗前后自身配对的血清样本20份,即入组口服吉非替尼前及临床评价为疾病进展前两周所采集的外周血血清。所有的患者对吉非替尼的最佳总疗效评价为疾病稳定或部分缓解。所有样本用弱阳离子微珠进行预分离后,在Bruker AutoflexTM基质辅助激光解析离子化-时间飞行质谱仪(MALDI-TOF-MS)上进行血清蛋白质谱检测。以ClinProTools(Version:2.1)软件进行数据采集分析。结果自身配对分析发现有7个血清蛋白质表达水平在肺癌患者耐药前后的血清中有统计学差异。该7个血清蛋白质谱峰为3242.09、8690.36、2952.64、3224.04、1450.51、1887.8及3935.73(m/z)。有3个血清蛋白(3242.09、2952.64及3224.04)在耐药血清中下调,其余4个血清蛋白(8690.36、1450.51、1887.8及3935.73)则出现上调。结论特定的血清差异蛋白可能与吉非替尼治疗有效患者在治疗过程中出现耐药相关。这些差异蛋白的特性及其与吉非替尼治疗耐药的分子机制有待进一步研究。更多还原

【Abstract】 Background and objective All the advanced NSCLC patients that received EGFR-TKI therapy will eventually relapse after a period of efficacy.The aim of this study is to investigate the serum biomarkers as potential predictive factors for the efficacy of epidermal growth factor receptor(EGFR) tyrosine kinase inhibitor(TKI) targeted therapy in advanced non-small cell lung cancer.Methods Twenty self-paired serum samples were collected from 9 advanced NSCLC patients that evaluated as disease control(SD or PR) after gefinitib therapy,at the time points of before and after gefinitib treatment but 2 weeks before being evaluated as disease progress.All samples were pre-separated by WCX microbeads,and then detected on the MALDI-TOF-MS platform of Bruker AutoflexTM.ClinProTools(Version:2.1) was used to analyze the differentially expressed proteins.Results There were 7 protein peaks(m/z),3 242.09,8 690.36,2 952.64,3 224.04,1 450.51,1 887.8 and 3 935.73 found statistically differentially expressed between the self-paired samples.Three proteins(3 242.09,2 952.64 and 3 224.04) were down-regulated and four proteins(8 690.36,1 450.51,1 887.8 and 3 935.73) up-regulated in gefinitib treated sera.Conclusion The data here suggest that several specific protein peaks might indicate gefinitib resistance,yet the identities of these proteins and the mechanisms underlying the responsiveness to gefinitib treatment need further investigation.更多还原