血清多肽谱对高级别浆液性卵巢癌诊断价值分析

目的寻找高级别浆液性卵巢癌相关的血清标志,并评价其诊断价值。方法收集2006-07-17-2011-03-30浙江省肿瘤医院卵巢癌血清样本165例,均经病理确诊。采用纳米磁珠结合基质辅助激光解析离子化飞行时间质谱（MALDI-TOF-MS）技术,检测95例高级别浆液性卵巢癌患者、34例其他上皮性卵巢癌患者、36例卵巢良性肿瘤患者和70名健康志愿者血清样本,并获得血清多肽谱。采用Biomarker Wizard软件分析所获得的多肽谱找出差异蛋白,进一步采用SPSS 12.0中ROC曲线分析差异蛋白,评价其诊断灵敏度和特异性。结果通过34例高级别浆液性卵巢癌患者和34名年龄匹配的健康人群血清多肽谱比较筛选出8个差异峰,P〈0.0001。进一步扩大样本量,经分析ROC曲线面积〉0.9的有2 742、8 568和8 692m/z 3个差异峰;当差异峰2 742m/z取临界值24.31时,其诊断敏感性和特异性分别为90%和84.2%,其中早期卵巢癌诊断敏感性为82.35%。早期（Ⅰ、Ⅱ）与晚期（Ⅲ、Ⅳ）高级别浆液性卵巢癌比较有3 163、4 180和4 288m/z 3个差异峰,P〈0.01,其ROC曲线面积均〉0.7;其中3 163m/z鉴别早晚期高级别浆液性卵巢癌敏感性和特异性分别为52.9%和88.5%。高级别浆液性卵巢癌患者与其他上皮性卵巢癌患者比较无明显差异峰。高级别浆液性卵巢癌患者和卵巢良性肿瘤患者比较有13745、15930和28111m/z 3个差异峰,P〈0.01,ROC曲线面积〉0.7的差异峰有15930和28 111m/z;其中15930 m/z的鉴别诊断敏感性和特异性分别达到52.6%和80.6%。结论 2 742m/z差异蛋白对于早期高级别卵巢癌具有较高的诊断价值,3163m/z在早期和晚期高级别浆液性卵巢癌患者的鉴别诊断中有一定价值,15930m/z对于高级别浆液性卵巢癌和良性卵巢肿瘤鉴别诊断有一定的价值。

Serum protein profiling application value in high-grade-serous ovarian cancer diagnosis

OBJECTIVE To analyze the serum proteomic patterns in the high-grade-serous ovarian cancer patients using magnetic bead with MALDI-TOF,and evaluate its clinic significance.METHODS Collection of 165 ovarian cancer serum samples from 2006-07-17 to 2011-03-30 in Zhejiang cancer hospital,all diagnosed by pathology.WCX magnetic bead and MALDI-TOF-MS were used to detect the serum proteome patterns of 129 patients with ovarian carcinomas,36 patients with benign ovarian disease and 70 healthy women.Biomarker Wizard software was used to detect significantly different protein peaks between ovarian cancer and controls.The SPSS 12 ROC curve analysis of differential protein was used to evaluate its diagnostic sensitivity and specificity.RESULTS Eight protein peaks were significantly different between ovarian carcinomas and controls,P〈0.000 1.Further expanding the sample size,the ROC curve area of 2742,8568 and 8692m/z exceeded to 0.9.When different peak 2742m/z cutoff value was 24.31,the diagnostic sensitivity and specificity were 90% and 84.2%,the sensitivity to early diagnosis of ovarian cancer was 82.35%.Three protein peaks were significantly different between early and late high-grade-serous ovarian cancer,P〈0.01.Their ROC curve area are greater than 0.7.The differential diagnostic sensitivity and specificity of 3163m/z were respectively 52.9% and88.5%.High-grade-serous ovarian cancer patients and other patients with epithelial ovarian cancer showed no significant different peaks.Three protein peaks were significantly different between high-grade-serous ovarian cancer and ovarian benign tumor patients,P0.01.The ROC curve area of 15 930 and 28 111m/z exceeded 0.7.The differential diagnostic sensitivity and specificity of 15 930m/z were respectively 52.6%and 80.6%.CONCLUSION Protein 2 742m/z has relatively high value for early diagnos of high-grade-serous ovarian cancer,3 163m/z has a certain value in the differential diagnosis of early and late high-grade-serous ovarian cancer patients.15 930m/z has a certain value for