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

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

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盲筛验证。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。

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.