目的 研究血清人附睾蛋白4（human epididymal protein，HE4）联合外泌体中的微小RNA（miRNA）-200a/200b/200c用于糖链抗原125（sugar chain antigen，CA125）阴性卵巢上皮癌（epithelial ovarian carcinoma，EOC）早期诊断的价值。 方法 选取CA125阴性EOC患者120例作为研究对象，设为研究组；另选取同期收治的115例卵巢上皮良性肿瘤患者作为良性组，107例于武汉市第一医院体检的健康女性作为对照组。比较3组HE4、CA125、miRNA-200a、miRNA-200b、miRNA-200c水平，通过受试者工作特征（ROC）曲线分析各项血清指标鉴别CA125阴性EOC及卵巢上皮良性肿瘤的价值。 结果 研究组HE4及miRNA-200a、miRNA-200b、miRNA-200c水平显著高于良性组、对照组，差异有统计学意义（P < 0.05）。经ROC分析证实，血清HE4及miRNA-200a、miRNA-200b、miRNA-200c能够用于CA125阴性EOC的诊断，且HE4+miRNA-200a/b/c联合诊断相对于单独及两两诊断可获得更高的曲线下面积，均有P < 0.05。经logistic逐步回归分析证实，HE4 ≥ 163.110 pmol/L、miRNA-200a ≥ 2.700 2^-△△CT、miRNA-200b ≥ 1.665 2^-△△CT、miRNA-200c ≥ 1.395 2^-△△CT为CA125阴性EOC发生的危险因素（P < 0.05）。 结论 血清HE4及miRNA-200a、miRNA-200b、miRNA-200c可用于CA125阴性EOC的早期诊断中，且四项指标联合诊断具有更高的敏感度与特异性，值得临床医师关注。

Objective To investigate the value of serum human epididymal protein 4 （HE4） combined with micrornas （mirnas） -200a/200b/200c in exosomes in the early diagnosis of glycochain antigen 125 （CA125） negative epithelial ovarian carcinoma （EOC）. Methods A total of 120 patients with CA125-negative EOC were selected as the study group， and 115 patients with ovarian epithelial benign tumor admitted during the same period were selected as the benign group. Another group of 107 healthy women who underwent physical examination in wuhan firsthospital were selected as the control group. The levels of HE4， CA125， miRNA-200a， miRNA-200b and miRNA-200c were compared among the three groups. The value of serum indexes in differentiating CA125-negative EOCs and benign ovarian epithelial tumors was analyzed by receiver operating characteristic （ROC） curve. Results The levels of HE4， miRNA-200a， miRNA-200b and miRNA-200c in the study group were significantly higher than those in the benign group and control group， statistically significant differences between the groups （P < 0.05）. ROC analysis confirmed that serum HE4， miRNA-200a， miRNA-200b， and miRNA-200c could be used for the diagnosis of CA125-negative EOC. The combined diagnosis by HE4+miRNA-200a/b/c could obtain a higher area under the curve than the single or pair-based diagnosis （P < 0.05）. Logistic stepwise regression analysis confirmed that， HE4 ≥ 163.110 pmol/L， miRNA-200a ≥ 2.700 2^-△CT， miRNA-200b ≥ 1.665 2^-△CT， miRNA-200c≥ 1.395 2^-△△CT were the risk factors for CA125-negative EOC （P < 0.05）. Conclusion Serum HE4， miRNA-200a， miRNA-200b and miRNA-200c can be used in the early diagnosis of CA125-negative EOC. The diagnosis with the four indicators combined has higher sensitivity and specificity.