血清糖类抗原125及人附睾蛋白4联合检测对卵巢上皮性癌的诊断价值

Diagnostic value of combined detection of carbohydrate antigen 125 and human epididymis protein 4 for epithelial ovarian cancer

目的探讨血清人附睾蛋白4(HE4)和糖类抗原125(CA125)联合检测对卵巢上皮性癌的诊断价值。方法收集2012年1月至2017年12月在山西省肿瘤医院因子宫附件肿物行手术治疗的患者,根据术后病理结果分为卵巢上皮性癌组494例和卵巢良性疾病组462例,采用酶联免疫吸附试验(ELISA)和化学发光免疫分析法检测两组患者血清HE4和CA125水平,分析HE4和CA125单独及联合检测对卵巢上皮性癌的诊断价值。结果卵巢上皮性癌组血清CA125、HE4水平[中位值(P25,P75)]分别为273.34 U/ml(39.34 U/ml,709.74 U/ml)和199.08 pmol/L(75.81 pmol/L,449.20 pmol/L),高于卵巢良性疾病组的16.30 U/ml(6.30 U/ml,53.60 U/ml)和39.54 pmol/L(29.57 pmol/L,53.80 pmol/L),差异均有统计学意义(均P<0.05)。卵巢上皮性癌组血清CA125与HE4水平呈正相关(r=0.481,P<0.01)。Ⅲ、Ⅳ期卵巢上皮性癌中血清CA125和HE4水平均高于Ⅰ、Ⅱ期(均P<0.05);与中、高分化患者相比,低分化患者中两者水平均最高(均P<0.05)。血清HE4单独检测诊断卵巢上皮性癌的特异度、阳性预测值均高于CA125(均P<0.01)。与HE4单独检测相比,CA125与HE4联合检测时灵敏度升高(P=0.004),特异度降低(P=0.044)。取CA125和HE4两者均为阳性表示阳性结果,与HE4单独检测相比,其特异度和阳性预测值升高(均P<0.01),但灵敏度下降(P<0.01);在CA125+HE4-患者中,灵敏度和特异度均下降,而在CA125-HE4+患者中,特异度升高,但差异无统计学意义(P=0.892);取CA125和HE4两者中其一阳性表示阳性结果,灵敏度和阴性预测值升高(均P<0.01),但特异度和阳性预测值均下降(均P<0.01)。血清CA125和HE4联合检测的曲线下面积为0.911,其临床诊断价值优于两者单独检测。结论在卵巢上皮性癌的诊断中,血清HE4的特异度高于CA125,但灵敏度低于CA125,两者联合检测更有利于提高卵巢上皮性癌的诊断准确率。

Objective To explore the diagnostic value of combined detection of serum human epididymis protein 4(HE4)and carbohydrate antigen 125(CA125)for ovarian epithelial cancer.Methods Patients who underwent surgery for the adnexal tumor at Shanxi Provincial Cancer Hospital from January 2012 to December 2017 were enrolled.According to the postoperative pathological results,these patients were divided into the ovarian epithelial cancer group(494 cases)and benign ovarian disease group(462 cases).The serum expressions of HE4 and CA125 in the two groups were detected by enzyme-linked immunosorbent assay(ELISA)and chemiluminescence immunoassay.The diagnostic value of detection of HE4 and CA125 alone or in combination for ovarian epithelial cancer was analyzed.Results The median levels(P 25-P 75)of serum CA125 and HE4 in ovarian epithelial cancer group were 273.34 U/ml(39.34 U/ml,709.74 U/ml)and 199.08 pmol/L(75.81 pmol/L,449.20 pmol/L),which were higher than those in ovarian benign disease group[16.30 U/ml(6.30 U/ml,53.60 U/ml)and 39.54 pmol/L(29.57 pmol/L,53.80 pmol/L)](both P<0.05).There was a positive correlation between serum CA125 and HE4 levels in ovarian epithelial cancer group(r=0.481,P<0.01).Serum CA125 and HE4 levels in patients with stageⅢandⅣwere higher than those in patients with stageⅠandⅡ(both P<0.05),and serum CA125 and HE4 levels in patients with poor differentiation were higher than those in patients with moderate differentiation(P<0.05).Compared with CA125,the specificity and positive predictive value of serum HE4 for the diagnosis of ovarian epithelial cancer were higher(both P<0.01).Compared with HE4 alone,the sensitivity of CA125 combined with HE4 increased(P=0.004)and the specificity decreased(P=0.044).When both CA125 and HE4 were positive for positive results,compared with HE4 alone,the specificity and positive predictive value increased(both P<0.01),but the sensitivity decreased(both P<0.01).In patients with CA125+HE4-,the sensitivity and specificity decreased,while in CA125-HE4+patients,the specificity was elevated,but the difference was not statistically significant(P=0.892).When one of CA125 and HE4 was positive for positive results,the sensitivity and negative predictive value increased(both P<0.01),but the specificity and positive predictive value decreased(both P<0.01).The area under the curve of serum CA125 and HE4 combined detection was 0.911,indicating its clinical diagnostic value was better than that of the two alone.Conclusions In the diagnosis of epithelial ovarian cancer,the specificity of serum HE4 is higher than that of CA125,but the sensitivity is lower than that of CA125.The combined detection of HE4 and CA125 is more conducive to improve the diagnostic accuracy of ovarian epithelial cancer.