血清蛋白质指纹图谱筛选上皮性卵巢癌及预测肿瘤复发的应用研究

目的:建立人上皮性卵巢癌蛋白质组诊断模型,并盲法验证.方法:应用蛋白质芯片SELDI-TOF MS技术和生物信息学方法,比较40例上皮性卵巢癌患者手术前后、29例卵巢癌复发患者、22名健康人血清蛋白质谱,用45例包括良恶性卵巢病变患者和健康人的血清作肓筛验证.结果:卵巢癌和正常人血清比较,P＜0.01的差异蛋白峰有7个,用其中的质荷比4 162.69、5 804.26、6 749.37建立诊断模型,诊断的敏感度为98.3％,特异度为95.7％,阳性预测值为96.7％.卵巢癌术前、术后血清蛋白质谱比较,P＜0.01的差异蛋白峰有4个,术后化疗后复发与正常人血清差异蛋白质峰有5个,其中质荷比5 804.26蛋白峰术后下降、复发时升高.结论:应用SELDI方法建立人卵巢癌血清蛋白质谱诊断模型可用于卵巢癌的筛查,质荷比5 804.26蛋白峰有望成为卵巢癌疗效监测特异蛋白峰.

Application of Serum Protein Profiling in the Diagnosis of Epithelial Ovarian Cancer

Objective: To develop the rationales for ovarian cancer-specific protein profiles in serum.Methods: Serum protein profiles from 40 epithelial ovarian cancer cases and 29 recurred ovarian cancer cases were compared with 22 healthy controls using surface-enhanced laser desorption ionization time-of-flight mass spectrometry(SELDI-TOF-MS).Blinded test was conducted subsequently for identification of the protein pattern.The spectra were analyzed statistically between positive and negative groups.Results: Seven peaks were significantly different between ovarian cancer and healthy controls(P<0.01,6 peaks up-regulated and 1 down-regulated).A set of three peals,at 4162.69,5804.26,6749.37 m/z respectively,were selected as ovarian cancer biomarker,and the sensitivity and specificity was respectively 98.3% and 95.7%.Identification by blinded validation indicated a positive predictive value of 96.7%.Four peaks were significantly different between preoperative and operative ovarian cancer,five peaks were significantly different between recurred ovarian cancer and healthy controls.The peak with 5 804.26 was down-regulated in operative cases and up-regulated in recurred cases.Conclusion: The serum protein profiling can be a novel,effective and sensitive tool to screen for ovarian cancer and establish a diagnostic model.