应用血清蛋白质指纹图谱筛选上皮性卵巢癌及预测肿瘤耐药性的研究  

Study for drug-resistance of epithelial ovarian cancer by serum protein profiling

作　　者：张文颖 朱丽荣[4] 郑燕华 周玲 张建中 吴久鸿 廖秦平[4] 

机构地区：[1]解放军三0六医院妇产科,北京100101 [2]解放军三0六医院病理实验科,北京100101 [3]解放军三0六医院药学部,北京100101 [4]北京大学第一医院妇产科

出　　处：《中华医学杂志》2009年第19期1326-1329,共4页National Medical Journal of China

摘　　要：目的建立卵巢癌蛋白质组诊断模型，并经过盲法验证。在此基础之上，比较分析多药耐药基因糖蛋白MDRl和多药耐药相关蛋白MRP阳性和阴性组的血清蛋白质指纹。方法应用蛋白质芯片SELDI-TOFMS技术和生物信息学方法，比较36例上皮性卵巢癌患者和30名健康人血清蛋白质谱，用30例包括良恶性卵巢瘤患者和健康人的血清作盲筛验证。同时利用免疫组化方法检验MDRl和MRP在上皮性卵巢癌组织的表达，进而分析耐药蛋白阳性和阴性组的血清蛋白质谱。结果卵巢癌和正常血清比较，值P〈0．01的差异峰有29个，15个峰上调，14个峰下调。用其中的3个标志蛋白建立诊断模型（相对分子质量为5486、6463及8575），该诊断模型的敏感性100％，特异性93．33％。盲筛验证表明阳性预测值90％。卵巢癌组织MDRl阳性率69．4％。阳性与阴性组血清蛋白质谱比较，P〈0．01的差异蛋白质峰有20个。MRP阳性率63．8％。P〈0．01的差异蛋白质峰有1个。结论应用SELDI方法建立卵巢癌血清蛋白质谱诊断模型是实现卵巢癌筛查的理想途径；并且能够明确的将多药耐药的病例筛选出来，MDRl免疫组化结果可以做为筛选卵巢癌耐药病例的建模依据。Objective To develop the rationales for ovarian cancer-specific protein profiles in serum and to analyze the protein profiles of multidrug resistance P-glueoprotein （ MDR1 ） and muhidrug resistanceassociated protein （MRP）positive and negative expression sets for a rapid and sensitive serum protein pattern. Method Serum protein profiles from 36 epithelial ovarian cancer eases were compared with 30 healthy controls using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry （ DELD1- TOF-MS）. Blinded test was conducted subsequently for identification of the protein pattern. Expression of MDR and MRP were detected in set of training cases by immunohistochemistry. The spectra were analyzed statistically between positive and negative groups. Results Twenty-nine peaks were significantly different between ovarian cancer and healthy controls （P 〈 0. O1, 15 peaks up-regulated and 14 down-regulated）. A set of three peaks, at 5 486, 6 463 and 8 575 m/z respectively, were selected from 29 sense peaks as an ovarian cancer biomarker. The sensitivity was 100% and specificity 93.33%. Identification by blinded validation indicated a positive predictive value of 90%. MDR1 expression in ovarian cancer was 69. 4 %. Twenty peaks were significantly different between positive and negative sets （ P 〈 0. 01 ）. MRP expression in ovarian cancer was 63.8%. But one peak was detected （P 〈0. 01 ）. Conclusion It was an ideal pattern for employing the SELDI mass spectrum approach to diagnose ovarian cancer and select the multidrug resistance cases. Serum biomarkers for detecting drug resistance in ovarian cancer can be established on the basis of MDR1 immunohistoehemist

关 键 词：卵巢癌 蛋白质组学 耐药 MDRl 

分 类 号：R686[医药卫生—骨科学]