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
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MDR1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-TOF MS技术和生物信息学方法 ,比较36例上皮性卵巢癌病人和30例正常人血清蛋白质谱,用30例包括良恶性卵巢瘤病人和正常人的血清作盲筛验证.同时利用免疫组化方法 检验MDR1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MDR1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,MDR1免疫组化结果 可以做为筛选卵巢癌耐药病例的建模依据.
更多Objective To develop an ovarian cancer-specific protein profiles in serum.On the basis, to analyze the protein profiles of multidrug resistance P-glucoprotein (MDR1)and multidrug resistance-associated protein (MRP) positive and negative expression sets for a rapid and sensitive serum protein pattern.Method Serum protein profiles from 36 epithelial ovarian cancer cases were compared with 30 healthy controls using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (DELDI-TOF-MS). Blinded test was done 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 29 peaks were significantly different between ovarian cancer and healthy controls (P<0.01, 15 peaks were up-regulated and 14 down-regulated). We selected a set of three peaks, at 5486, 6463 and 8575 m/z, from 29 sense peaks as ovarian cancer biomarker. It has a sensitivity of 100% and specificity of 93.33%. Identification by blinded validation indicated a positive predict value of 90%. MDR1 expression in ovarian cancer was 69.4 %. There 20 peaks were significantly different between positive and negative set (P<0.01). MRP expression in ovarian cancer was 63.8%. But there was just 1 peak detected (P<0.01).Conclusion It was an idealized pattern for applying SELDI mass spectrum approach to diagnosis of ovarian cancer. The multidrug resistance cases in ovarian cancer can be selected by it. Serum biomarker for detecting drug resistance in ovarian cancer could be established according to MDR1 immunohistochemistry.
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