卵巢癌患者绝经前后人附睾蛋白4、糖类抗原125的差异性及卵巢癌风险预测模型指数的早期诊断效能分析

Difference of human epididymis protein 4 and carbohydrate antigen 125 in patients with ovarian cancer before and after menopause

目的比较卵巢癌患者绝经前后人附睾蛋白4(human epididymis protein 4,HE4)和糖类抗原125(carbohydrate antigen 125,CA125)的差异,并评价卵巢癌风险预测模型(risk of ovarian malignancy algorithm,ROMA)指数的早期诊断效能。方法选择2018年4月至2019年9月期间在中国医科大学肿瘤医院住院治疗的236例卵巢癌(恶性卵巢肿瘤组)患者的临床资料进行回顾性分析,另选取同期治疗的良性卵巢肿瘤患者312例作为对照(良性卵巢肿瘤组)。在临床病理切片确认的基础上,分别采集患者的血清以检测HE4和CA125,同时依据公式计算得出ROMA;比较绝经前后HE4、CA125和ROMA指数的差异性,以及三者的ROC生存曲线的诊断效能,并且评价其在卵巢癌患者不同的临床特征之间的关系,以全面分析ROMA指数的早期诊断效能。结果在恶性卵巢肿瘤者血清中,HE4、CA125以及ROMA指数均异常高表达,且HE4绝经前[263.2(128.4,385.6)pmol/L]后[354.8(179.5,554.2)pmol/L]比较差异有统计学意义(Z=2.09,P=0.037);通过拟合ROC曲线:绝经前ROMA指数的AUC为0.939,绝经后ROMA指数的AUC为0.933,均高于HE4(0.937,0.906)和CA125(0.913,0.924),其分别对应的Youden正确诊断指数分别为0.800和0.742,均高于相应的HE4(0.788,0.653)和CA125(0.498,0.565)指标;HE4两分类与腹腔积液发生有关联[绝经HE4<140 nmol/L和未绝经HE4<70 nmol/L者占25.77%,绝经HE4≥140 nmol/L和未绝经HE4≥70 nmol/L者占74.23%],差异有统计学意义(χ^(2)=10.155,P=0.006);CA125与实质肿瘤最大直径分类、腹腔积液发生有关联,差异均有统计学意义(P均<0.05);ROMA指数与绝经与否、肿块最大直径分类、实质肿瘤最大直径分类、腹腔积液发生均有关联,差异均有统计学意义(P均<0.05)。结论ROMA指数针对于恶性卵巢癌尤其是绝经前的患者具有良好的诊断效能,对于卵巢癌的早期诊断有一定的指导价值,后续还会进一步开展验证性研究。

Objective To compare the difference of human epididymis protein 4(HE4)and carbohydrate antigen 125(CA125)indexes before and after menopause in ovarian cancer patients,and to evaluate the efficacy of risk of ovarian malignancy algorithm(ROMA)index in early diagnosis.Methods The clinical data of 236 patients with ovarian cancer(malignant ovarian tumor group)who were hospitalized in Cancer Hospital of China Medical University from April 2018 to September 2019 were retrospectively analyzed,and 312 benign patients treated at the same period were selected as the control group(benign ovarian tumor group).On the basis of clinical pathological section confirmation,the serum samples were collected to detect HE4 and CA125,and the ROMA index was calculated according to the formula.The differences of HE4,CA125 and ROMA indexes before and after menopause,as well as the diagnostic efficacy of ROC survival curve of the three were compared,and the relationship between the different clinical characteristics of ovocarcinoma patients was evaluated to comprehensively analyze the early diagnostic effect of ROMA index.Results In the serum of patients with malignant ovarian cancer,HE4,CA125 and ROMA index were abnormally high expression,and the difference between HE4 before(263.2(128.4,385.6)pmol/L)and after menopause(354.8(179.5,554.2)pmol/L)was statistically significant(Z=2.09,P=0.037).Through fitting the ROC curve:the AUC of premenopausal ROMA index was 0.939,and the AUC of postmenopausal ROMA index was 0.933,which were higher than HE4(0.937,0.906)and CA125(0.913,0.924),and their corresponding Youden correct diagnostic indexes were 0.800 and 0.742 respectively,which were higher than HE4(0.788,0.653)and CA125(0.498,0.565).The two categories of HE4 were associated with the occurrence of peritoneal effusion(the percentage of postmenopausal and premenopausal HE4<140 nmol/L and premenopausal HE4<70 nmol/L were 25.77%,74.23%and 74.23%respectively),and the difference was statistically significant(χ^(2)=10.155,P=0.006).CA125 was associated with the classification of the largest diameter of parenchymal tumor and the occurrence of peritoneal effusion(all P<0.05).ROMA index was associated with menopause or not,classification of maximum diameter of mass,classification of maximum diameter of parenchymal tumor and occurrence of ascites,and the differences were statistically significant(all P<0.05).Conclusion ROMA index has a good diagnostic efficiency in the diagnosis of malignant ovarian cancer,especially premenopausal patients with good diagnostic efficiency,for early diagnosis of ovarian cancer has a certain guiding value,the follow-up will further carry out confirmatory research.