转甲状腺素蛋白在诊断卵巢癌中的价值研究

Clinic diagnostic value of TTR in ovarian cancer

目的通过检测血清转甲状腺素蛋白(TTR)、血清人附睾蛋白4(HE4)及癌抗原125(CA125)水平评价TTR对诊断卵巢癌的临床价值。方法回顾性分析自2012年1月至2018年4月在浙江衢化医院妇科因附件包块住院手术且满足入选条件的146例患者临床资料,146例患者经术后病理明确诊断为卵巢恶性肿瘤106例,按照国际妇产科联盟(FIGO)2014分期标准,将Ⅰ～Ⅱ期40例设为早期卵巢癌组,Ⅲ～Ⅳ期66例设为晚期卵巢癌组,其中40例卵巢良性肿瘤设为良性肿瘤组,同时选取健康女性50例作为正常对照组。用电化学发光免疫法检测各组的血清TTR和HE4,用放射免疫法测定血清CA125,并对检测结果进行统计分析。结果卵巢良性肿瘤组与正常对照组的TTR和HE4水平比较差异均无统计学意义(均P>0.01),其他各组间的TTR、HE4及CA125水平比较差异均有统计学意义(t=-16.485～11.752,均P<0.01)。在不同期别卵巢癌ROC曲线下,早期卵巢癌(Ⅰ～Ⅱ期)AUC显示:HE4(0.969)>TTR(0.963)>CA125(0.810);晚期卵巢癌(Ⅲ～Ⅳ期)AUC显示:HE4(1.000)>CA125(0.999)>TTR(0.794),均P<0.01。早期卵巢癌诊断的理想截断值:TTR为214.50μg/mL,HE4为100.50pmol/L,CA125为35.50IU/mL);晚期卵巢癌诊断的理想截断值:TTR为210.00μg/mL,HE4为267.00pmol/L,CA125为105.00IU/mL。在各自的理想截断值下,早期卵巢癌诊断的敏感性:HE4为87.50%,TTR为84.40%,特异性:TTR+HE4和TTR+CA125均为100.00%,约登指数:HE4(0.83)>TTR+HE4(0.80);晚期卵巢癌诊断的敏感性:CA125、TTR+CA125和TTR+HE4+CA125均为98.50%,特异性:除TTR为58.60%外,其他均为100.00%,约登指数:CA125、TTR+CA125和TTR+HE4+CA125均为0.99。结论 TTR是一个相对独立的具有高敏感性和特异性的诊断早期卵巢癌的有效指标。

Objective To evaluate the clinic value of transthyretin (TTR) in diagnosis of ovarian cancer by monitoring the serum levels of TTR,human epididymis protein 4 (HE4) and cancer antigen 125 (CA125).Methods A retrospective analysis was carried out in 146 cases undergoing surgery in Zhejiang Quhua Hospital for adnexal mass during January 2012 to April 2018.Among them,106 cases were diagnosed with ovarian malignant tumor,including 40 cases at stage I-II in early ovarian cancer group and 66 cases at stage Ⅲ-Ⅳ in late ovarian cancer group according to FIGO 2014.Forty cases of ovarian benign tumor were set in benign tumor group.Another 50 healthy women were selected in control group.Serum level of TTR,HE4 and CA125 were detected by electrochemiluminescence immunoassay and radioimmunoassay,respectively for statistical analysis.Results The serum level of TTR and HE4 were not statistically different between benign tumor group and control group (both P >0.01),but the differences in TTR,HE4 and CA125 were significant among different groups ( t value ranged -16.485-11.752,all P <0.01).The area under the curve of ROC showed HE4 (0.969)>TTR (0.963)>CA125 (0.810) in early ovarian cancer (Ⅰ-Ⅱ) group and HE4 (1.000)>CA125 (0.999)>TTR (0.794) in late ovarian cancer (Ⅲ-Ⅳ) group (all P <0.01).The ideal cut-off value in diagnosis of early staging ovarian cancer was 214.50μg/mL (TTR),100.50 pmol/L (HE4) and 35.50IU/mL (CA125),respectively.And the ideal cut-off value in diagnosis of advanced staging ovarian cancer was 210.00μg/mL (TTR),267.00pmol/L (HE4) and 105.00IU/mL (CA125),respectively.According to different ideal cut-off value ,the sensitivity of diagnosis of early staging ovarian cancer was 87.50%(HE4) and 84.40%(TTR),the specificity was all 100%(TTR+HE4,TTR+CA125),and Youden index was HE4 (0.83)> TTR+HE4 (0.80).The sensitivity of diagnosis of advanced staging ovarian cancer was all 98.50%(CA125,TTR+CA125,TTR+HE4+CA125),the specificity was all 100.00% except for TTR (58.60%),and Youden index was all 0.99 (CA125,TTR+CA125,TTR+HE4+CA125).Conclusion TTR is an independent and effective marker with high sensitivity and specificity in diagnosis of early ovarian cancer.