血清人附睾蛋白4对妇女盆腔疾病的诊断价值

目的探讨血清人附睾蛋白4(HE4)对妇女盆腔疾病诊断的临床价值。方法分别采用酶联免疫吸附试验(ELISA)、免疫化学发光法测定43名健康妇女(正常对照组)和133例妇女盆腔疾病(包括卵巢癌7例、子宫恶性肿瘤40例、卵巢良性病变34例、子宫良性病变52例)患者血清HE4和糖类抗原125(CA125)水平。患者根据术后包块切片病理报告分组。以正常对照组x珋±2s作为正常参考范围,计算血清HE4和CA125水平对妇女盆腔恶性疾病的灵敏度和特异性等诊断性能。结果 HE4的正常参考范围上限为55.86 pmoL/L、CA125为35 kU/L。卵巢良性病变组、子宫良性病变组及正常对照组血清HE4及CA125水平差异无统计学意义(P>0.05);卵巢癌组患者HE4及CA125水平明显高于正常参考范围上限,且高于子宫恶性肿瘤、卵巢良性病变、子宫良性病变及正常对照组(P<0.01);子宫恶性肿瘤组血清HE4水平也高于正常参考范围上限,亦高于卵巢良性病变、子宫良性病变及正常对照组(P<0.05);但血清CA125水平4组间差异无统计学意义(P>0.05)。卵巢癌组和子宫恶性肿瘤组HE4与CA125呈正相关[相关系数(r)分别为0.467、0.380,P<0.05],其他3组之间无明显相关性。HE4和CA125在卵巢癌、子宫恶性肿瘤、卵巢良性性病变、子宫良性病变及正常对照组中的阳性率分别为100.00%、71.43%,37.50%、30.00%,14.70%、11.76%,19.23%、32.69%,2.32%、2.32%;HE4及CA125对卵巢癌的灵敏度分别为100.00%、71.43%,特异性为82.35%、85.29%,阳性预测值53.85%、50.00%,阴性预测值为100.00%9、3.50%;卵巢癌组HE4的受试者工作特征(ROC)曲线下面积(AUC)明显大于CA125(P<0.01)。将卵巢癌组和子宫恶性肿瘤组合并为盆腔恶性肿瘤组,血清HE4、CA125、HE4+CA125对其诊断的灵敏度分别为46.80%、36.17%、54.41%,特异性为82.60%、75.58%、47.22%,阳性预测值为59.50%、44.74%4、9.33%,阴性预测值为74.00%、68.42%、52.31%。结论血清HE4水平除了可以作为卵巢癌与部份子宫恶性肿瘤的辅助诊断标志物外,还应注意部份妇女盆腔良性疾病患者血清HE4水平也可增高。

Diagnosis value of human epididymis protein 4 in patients with gynecological pelvic lesions

Objective To investigate the clinical value of human epididymis protein 4(HE4)on diagnosing gynecological pelvic lesions.Methods The HE4 and carbohydrate antigen 125(CA125) levels in sera from 133 patients with gynecological pelvic lesions(ovarian cancer: 7 cases,intrauterine tumor: 40 cases,benign ovarian disease: 34 cases and benign uterus disease: 52 cases)and 43 healthy women(as the control group)were determined by enzyme-linked immunosorbent assay(ELISA) and chemiluminescence immunoassay,respectively.The patients were classified according to the postoperative pathology results.The control group′s ±2s was as the normal reference range,and the HE4 and CA125 levels were used to evaluate the sensitivity and specificity on diagnosing gynecological pelvic malignant lesions.Results The threshold values of serum HE4 and CA125 in the control group were 55.86 pmoL/L and 35 kU/L respectively.The levels of serum HE4 and CA125 had no statistical significance in the patients with benign ovarian disease,benign uterus disease and the control group(P>0.05),and the levels of serum HE4 and CA125 in patients with ovarian cancer were significantly higher than the normal reference range and those in patients with intrauterine tumor,benign ovarian disease,benign uterus disease and the control group(P<0.01).The levels of serum HE4 in patients with intrauterine tumor were significantly higher than the normal reference range and those in patients with benign ovarian disease,benign uterus disease and the control group(P<0.05).However,the levels of serum CA125 had no significant difference in the 4 groups(P>0.05).The levels of serum HE4 and CA125 had positive correlation[coefficient of correlation(r)=0.467 and 0.380,P<0.05]in the patients with ovarian cancer and intrauterine tumor,but there was no correlation among the other 3 groups.The positive rates of HE4 and CA125 in patients with ovarian cancer,intrauterine tumor,benign ovarian disease,benign uterus disease and the control group were 100.00%,71.43%;37.50%,30.00%;14.70%,11.76%;19.23%,32.69% and 2.32%,2.32% respectively.The sensitivities of HE4 and CA125 to ovarian cancr were 100.00% and 71.43%,the specificities were 82.35% and 85.29%,the positive predictive values were 53.85% and 50.00%,and the negative predictive values were 100.00% and 93.50%.The area under the receiver operating characteristic(ROC) curve(AUC)of HE4 was bigger than that of CA125 in patients with ovarian cancer(P<0.01).Merging the ovarian cancer group and the intrauterine tumor group as pelvic malignant lesion group,the diagnostic sensitivities of HE4,CA125 and HE4+CA125 were 46.80%,36.17% and 54.41%,the specificities were 82.60%,75.58% and 47.22%,the positive predictive values were 59.50%,44.74% and 49.33%,and the negative predictive values were 74.00%,68.42% and 52.31%.Conclusions Besides the serum level of HE4 is helpful in the diagnosis of ovarian cancer and intrauterine tumor,the levels of HE4 will increase in a part of benign gynecological pelvic lesion.