蛋白指纹图谱技术筛选非小细胞肺癌患者EGFR—TKI疗效相关血清标记物  

Screening serum molecular markers related to therapeutic effect of EGFR-TKI for non-small cell lung cancer by protein fingerprinting technique

作　　者：陈雪琴[1] 杨邵瑜[1] 潘月龙[1] 余捷凯[2] 李鑫[1] 王建[1] 马胜林[1] 

机构地区：[1]杭州市第一人民医院肿瘤科,310006 [2]浙江大学医学院附属第二医院肿瘤研究所

出　　处：《浙江医学》2012年第18期1487-1489,1493,共4页Zhejiang Medical Journal

基　　金：杭州市重大科技创新项目（20112313A01）

摘　　要：目的应用蛋白指纹图谱技术筛选晚期非小细胞肺癌（NSCLC）患者表皮生长因子受体酪氦酸酶抑制剂（EGFR-TKI）疗效相关的血清标记物。方法收集16例接受EGFR—TKI治疗的晚期NSCLC患者治疗前的血清，应用表面增强激光解吸电离飞行时间质谱仪（SELDI-TOF—MS）检测16份血清的蛋白质指纹图谱，用ProteinchipSoftware3．2软件采集数据，用ZJU—PDAS软件分析两组差异蛋白。结果根据RECIST标准，6例部分缓解及2例疾病稳定超过6个月进入敏感组．1例稳定小于6个月及7例进展患者进入耐药组。共检测到高质量的蛋白质峰136个，筛选出7个差异蛋白质峰（P〈0，05），质荷比（M／Z）分别为4662、2678、9602、2288、4100、11侣5、4606Da，与敏感组相比，耐药组中有5个蛋白上调（4662、9602、4100、11185、4606Da），有2个蛋白下调（2678、2288Da）。结论耐药组5个上调的蛋白可能是耐药蛋白。而2个下调的蛋白可能是TKI药物敏感的标志，但是这些蛋白的特性及TKI原发耐药的分子机制有待于进一步研究。Objective TO screen the potential serum molecular markers which were related to therapeutic effect of epidermal growth factor receptor （EGFR） tyrosine kinase inhibitor （TKI） for advanced non-small cell lung cancer （NSCLC） patients by means of protein fingerprinting technique. Methods Sixteen advanced NSCLC patients received target therapy of EGFR TKI. Serum protein profiles were detected using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry （SELDI-TOF MS）, The protein spectra were collected by Proteinchip Software 3.2 and analyzed with software ZJU-PDAS. Results According to RECIST criteria, 6 patients who had a partial response and 2 patients who had stable disease for more than 6 months were classified into TKI sensitive group, 1 patients who had stable disease less than 6 months and 7 patients who had progressive diseasewere classified into TKI resistant group. One hundred and thirty-six mass peaks were detected from all pa- tients by receiver operator characteristic curve and seven differential protein peaks were found. Compared to the TKI sensitive group, 5 protein peaks with mass/charge ratios （M/Z） of 4 662, 9 602, 4 100, 11 185 and 4 606 were up-regulated and 2 peaks with M/Z of 2 678, 2 288 were down-regulated in the TKI resistant group. Conclusion Results indicate that 5 up-regulated serum protein peaks may be related to drug-resistance and 2 down-regulated protein peaks may be related to EGFR TKI sensitivity in advanced NSCLC patients. Further studies are needed for characterization of these proteins and the mechanism associated with TKI-resistance in NSCLC patients.

关 键 词：血清蛋白质谱 肺恶性肿瘤 靶向治疗 

分 类 号：R730.43[医药卫生—肿瘤]