血清人附睾分泌蛋白4和CA125水平检测在卵巢恶性肿瘤中的诊断价值

The values of serum human epididymis secretory protein 4 and CA125 assay in the diagnosis of ovarian malignancy

目的探讨血清人附睾分泌蛋白4（HFA）和CA125水平检测在卵巢恶性肿瘤诊断中的价值。方法用酶联免疫吸附试验方法对卵巢恶性肿瘤组（30例）、盆腔良性疾病组（110例，其中卵巢良性肿瘤45例、子宫内膜异位症和子宫腺肌病57例和盆腔炎8例）和正常组（137例）妇女血清中HE4和CA125水平进行双盲检测，结果以中位数表示，分析两指标单独或联合检测诊断卵巢恶性肿瘤的价值。血清HFA和CA。正常值分别为0—150pmol／L和0—35kU／L，单独或联合检测时，其中任一指标高于正常值即定为阳性。结果（1）卵巢恶性肿瘤组血清HE4和CA125水平分别为244pmol／L和601kU／L，分别与盆腔良性疾病组（分别为32pmol／L和22kU／L）和正常组（分别为32pmol／L和11kU／L）比较，差异均有统计学意义（P〈0．05）。卵巢恶性肿瘤组血清HFA单项检测的阳性率为63．3％，明显低于血清CA125单项检测的阳性率（86．7％，P=0．036）。（2）单项检测时，以盆腔良性疾病组作参照人群时，HE4和CA125单项检测的受试者工作特征曲线下面积（ROC—AUC）分别为0．900和0．840，其特异度为100％时的敏感度分别为70％和7％，两者比较，差异有统计学意义（P=0．000）；以正常组作参照人群时，HE4和CA125单项检测的ROC—AUC分别0．904和0．914，其特异度为100％时的敏感度分别为67％和87％，两者比较，差异有统计学意义（P=0．031）。（3）联合检测时，以盆腔良性疾病组作参照人群时，HFA＋CA125联合检测和CA125单项检测的ROC-AUC分别为0．894和0．840，其特异度为100％时的敏感度分别为50％和7％，两者比较，差异有统计学意义（P=0．000）。以正常组作参照人群时，HE4＋CA125联合检测和HE4单项检测的ROC—AUC分别为0．914和0．904，其特异度为100％时的敏感度分别为87％和67％，两者比较，差异有统计学意义（P=0．031）。以盆腔良性疾病组作参照人群时，HE4＋CA125联合检测在特异度为100％时的敏感度（50％）虽然低于HFA单项检测（70％），但两者比较，差异无统计学意义（P=0．070）。（4）以ROC曲线最左上方的点86pmol／L、正常组95％参考值50pmol／L和正常值的上限150pmol／L为界值点，比较HFA单项检测对卵巢恶性肿瘤的诊断能力，结果显示，界值点为50pmol／L时的特异度和阳性预测值分别为95％和63％，明显低于界值点为86（分别为100％和95％）和150pmol／L（均为100％）时的特异度和阴性预测值（P〈0．01）。结论HFA单项检测诊断卵巢恶性肿瘤的特异度优于CA125单项检测，两者联合检测可以提高诊断能力。以150pmol／L为界值点，对卵巢恶性肿瘤的诊断正确率更高，而以86pmol／L为界值点有利于卵巢恶性肿瘤的筛查、降低漏诊率。

Objective To evaluate the value of human epididymis secretory protein 4 （HE4）and CA125 in the diagnosis of ovarian malignancy. Methods HE4 and CA125 in the serum specimens of malignant ovarian tumor group（30 cases）, benign ovarian diseases （110 cases; 45 benign ovarian tumor, 57 endometriotic diseases and 8 pelvic inflammation were included） and healthy women group（ 137 cases）were assayed double blindly . The levels and the diagnosis efficiency of the HE4 and CA125 were analyzed. Results （1） The median levels of HE4 and CA125 were significantly higher in malignant ovarian tumor group （244 pmol/L and 601 kU/L respectively） than those of the benign ovarian diseases group（ 32 pmol/L and 22 kU/L respectively）and healthy women group （32 pmol/L and 11 kU/L respectively） （P =0. 000 - 0. 029）. The median levels of CA125 were also higher in endometriotic diseases and pelvic inflammation groups（53 and 41 kU/L respectively ）than those of benign ovarian tumor group and healthy women group （ 12 and 11 kU/L respectively ; P = 0. 000 - 0. 031 ）. （ 2 ） The positive rate of HE4 was lower than that of CA125 in malignant ovarian tumor group （ P = 0. 036 ）. HE4 was negative in benign diseases and healthy women groups. But the positive rates of CA125 were 56. 1% and 5/8 respectively in endometriotic diseases and pelvic inflammation groups and there were significant differences compared with HE4 （P = 0. 000）. （3） The HE4 assay had advantage over the CA125 assay in receiver operating characteristic-area under the curve （ROC-AUC） and sensitivity with a specificity of 100% when ovarian malignancy was compared with controls having benign diseases and healthy women, benign tumor or benign diseases groups respectively. The CA125 assay had advantage over the HE4 assay in ROC-AUC and sensitivity with the same specificity when ovarian cancers were compared with controls having healthy women group. （4） Combined assay of HE4 and CA125 was better than CA125 alone when ovarian malignancy was compared with controls having any group. （5） Combined assay was better than HE4 alone in ROC-AUC and sensitivity with the same specificity when ovarian cancers were compared with controls having benign diseases and healthy women or healthy women groups. And combined assay was lower in the ROC-AUC and the sensitivity with specificity of 100% than HE4 when ovarian cancers were compared with controls having benign tumors or benign diseases groups respectively. （6） The diagnosis efficiency of the HE4 assay at the level 86 pmol/L determined in ROC curve with controls having benign diseases and healthy women group and at the 95% reference level 50 pmol/L of healthy women or 150 pmol/L recommended by the kit respectively was compared. The sensitivity of 50 pmol/L was 73% higher than 150 pmol/L and 86 pmol/L, while the specificity and positive predictive value were lower （ P = 0. 002, P = 0. 000 ）. The specificity, accuracy and positive predictive value of HE4 assay at the set point of 150 pmol/L and 86 pmol/L were 100%, 96% and 96%. The set point of 86 pmol/L had advantage over 150 pmol/L at the sensitivity of diagnosis, 70% and 63% respectively. But the positive predictive value was 95% lower than 150 pmol/L, being 100%. There was no significant difference（ P = 0. 883 ,P = 0. 883 ）. Conclusions The specificity of HE4 assay is higher than CA125 assay in the diagnosis of ovarian cancer and HE4 combined with CA125 assay can improve the diagnoses. The set point of 150 pmol/L is advantageous for the accurate diagnosis, while the set point of 86 pmol/L is advantageous for the screening of malignant ovarian cancer.