血清间皮素、HE4、CA125及VEGF-C对卵巢癌的诊断价值研究

Clinical diagnostic value of serum mesothelin, HE4, CA125 and VEGF-C in ovarian cancer

目的探讨血清间皮素、人附睾上皮分泌蛋白4(HE4)、癌胚抗原125(CA125)及血管内皮生长因子C(VEGF-C)对卵巢癌的诊断价值。方法比较卵巢癌组(97例)、良性组(100例)及对照组(120例)的血清间皮素、HE4、CA125及VEGF-C水平。联合Logistic回归分析和ROC曲线比较单一和联合指标对卵巢癌的诊断效能,并进一步建立卵巢癌的偏最小二乘判别分析(PLS-DA)模型。结果卵巢癌组的血清间皮素、HE4、CA125和VEGF-C水平高于良性组和对照组,差异有统计学意义(P<0.05)。血清间皮素、HE4、CA125和VEGF-C的ROC曲线下面积(AUC)分别为0.78(95%CI:0.72,0.84)、0.90(95%CI:0.85,0.94)、0.88(95%CI:0.83,0.92)和0.84(95%CI:0.80,0.90)。检测血清标志物(间皮素+HE4+CA125+VEGF-C)的AUC与间皮素+HE4+CA125、HE4+CA125+VEGF-C及HE4+CA125相当(0.99、0.98、0.98和0.97)。基于血清HE4+CA125的PLS-DA模型诊断卵巢癌的敏感性、特异性和准确率分别为88.7%,97.7%和95.0%。基于血清间皮素+HE4+CA125+VEGF-C诊断卵巢癌的敏感性、特异性和准确率分比为91.8%,97.3%和95.6%。结论联合检测血清标志物HE4和CA125是经济、有效的组合模式,有助于卵巢癌的鉴别诊断。

Objective To evaluate the diagnostic value of serum mesothelin, human epididymis protein 4 （HE4）, cancer antigen 125 （CA125） and vascular endothelial growth factor C （VEGF-C） for patients with ova- rian cancer. Methods Serum levels of mesothelin, HE4, CA125 and VEGF-C in 97 cases of ovarian cancer, 100 cases of benign ovarian diseases and 120 healthy controls were analyzed. The logistic regression analysis and the receiver operating characteristic （ROC） curves were used to evaluate the individual and combined diag- nostic values of serum mesothelin, HE4, CA125 and VEGF-C for patients with ovarian cancer. And the diag- nostic model of partial least square discrininant analysis （PLS-DA） was established. Results Serum levels of mesothelin, HE4, CA125 and VEGF-C in the patients with ovarian cancer were significantly higher than those in the patients with ovarian benign diseases and healthy controls （P〈 0.05）. The area under the ROC （AUC） of serum mesothelin, HE4, CA125 and VEGF-C was 0.78 （95% CI： 0.72, 0.84）, 0.90 （95% CI： 0.85, 0.94）, 0.88 （95% CI： 0.83, 0.92） and 0.84 （95% CI： 0.80, 0.90）, respectively. The AUCs of the combined serum tumor markers （HE4＋CA125）, （mesothelin＋HE4＋CA125）, （HE4＋CAI25＋VEGF-C） and （mesothelin＋HE4＋ CA125＋ VEGF-C） was similar （0.97, 0.98, 0.98 and 0.99 respectively）. The sensitivity, specificity and the ac-curacy of the combined serum tumor markers （HE4＋CA125） for the diagnosis of ovarian cancer in the PLS-DA model were 88.7%, 97.7% and 95.0%, respectively. The sensitivity, specificity and the accuracy of combined serum tumor markers （mesothelin＋HE4＋CA125＋VEGF-C） for the diagnosis of ovarian cancer were 91.8%, 97.3% and 95.6%, respectively. Conclusions The combination of serum biomarkers （HE4＋CA125） is economical and effective, which is helpful for the diagnosis of ovarian cancer.