WFDC2编码的HE4在肺癌诊断和疗效监测中的应用价值

doi:10.3969/j.issn.1673-8640.2018.06.010

摘要/Abstract

摘要：

目的通过检测WFDC2编码的人附睾蛋白4（HE4）在肺癌患者血清中的表达水平,探讨其在肺癌早期诊断和疗效监测中的临床应用价值。方法选取226例肺癌患者（肺癌组）、128例肺部良性疾病患者（良性疾病对照组）以及100名正常人（正常对照组）为研究对象,用酶联免疫法检测血清WFDC2编码的HE4水平,同时用化学发光法检测血清癌胚抗原（CEA）、细胞角蛋白19片段（CYFRA21-1）、神经元特异性烯醇化酶（NSE）、鳞状细胞癌（SCC）相关抗原水平,并进行各组间的比较,采用受试者工作特征（ROC）曲线分析HE4、CEA、CYFRA21-1、NSE、SCC相关抗原和指标Logistic回归联合参数的曲线下面积（AUC）。结果肺癌组血清HE4水平[93.29（61.74,160.28）pmol/L]较良性疾病对照组[76.47（55.35,129.85）pmol/L]和正常对照组[45.64（36.60,62.35）pmol/L]升高（P<0.05）。不同病理类型肺癌患者血清HE4水平差异无统计学意义（P>0.05）。在诊断肺癌时,HE4的AUC为0.860,诊断效能最优,且HE4、CEA、CYFRA21-1、NSE、SCC相关抗原5项联合诊断的AUC（0.906）高于其中任意单项指标。不同临床分期肺癌患者血清HE4水平差异有统计学意义（P<0.05）,化疗后肺癌疾病进展患者血清HE4水平升高（P<0.05）。结论 WFDC2编码的HE4可以作为肺癌早期诊断的指标,在疗效监测方面也有一定的辅助作用。

关键词: 人附睾蛋白4, 肺癌, 诊断, 治疗效果

Abstract:

Objective To investigate the role of WFDC2 encoding human epididymis protein 4（HE4） in the early diagnosis and curative effect monitoring of pulmonary carcinoma. Methods A total of 226 pulmonary carcinoma patients（pulmonary carcinoma group）,128 patients with benign pulmonary disease（benign disease control group） and 100 healthy subjects（healthy control group） were enrolled. WFDC2 encoding HE4 was determined by enzyme immunoassay. The levels of carcinoembryonic antigen（CEA）,cytokeratin 19 fragment（CYFRA21-1）,neuron-specific enolase（NSE） and squamous cell carcinoma（SCC） related antigen were determined by chemiluminescence. The areas under receiver operating characteristic（ROC）curves（AUC） of HE4,CEA,CYFRA21-1,NSE and SCC related antigen in the 3 groups were evaluated. Results Serum HE4 level of pulmonary carcinoma group was 93.29（61.74,160.28） pmol/L,which was higher than those of benign disease control group [76.47（55.35,129.85） pmol/L] and healthy control group [45.64（36.60,62.35） pmol/L]（P<0.05）. There was no statistical significance for serum HE4 level with different pathological types of pulmonary carcinoma（P>0.05）. In the diagnosis of pulmonary carcinoma,the AUC of HE4 was 0.860,and HE4 had good diagnostic efficiency. The AUC of HE4 combined with CEA,CYFRA21-1,NSE and SCC related antigen was 0.906,which was higher than those of 5 single determinations. There was statistical significance for serum HE4 levels with different clinical stages of pulmonary carcinoma（P<0.05）. Serum HE4 levels were elevated after chemotherapy（P<0.05）. Conclusions WFDC2 encoding HE4 can be used as a marker for the early diagnosis and curative effect monitoring of pulmonary carcinoma.

Key words: Human epididymis protein 4, Pulmonary carcinoma, Diagnosis, Curative effect

中图分类号:

R446.62

罗佳龄, 彭霞, 林堃, 李莉. WFDC2编码的HE4在肺癌诊断和疗效监测中的应用价值[J]. 检验医学, 2018, 33(6): 508-511.

LUO Jialing, PENG Xia, LIN Kun, LI Li. WFDC2 encoding HE4 in the diagnosis and curative effect monitoring of pulmonary carcinoma[J]. Laboratory Medicine, 2018, 33(6): 508-511.

图/表 5

参考文献 10

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组别	例数	HE4
正常对照组	100	45.64（36.60,62.35）
良性疾病对照组	128	76.47（55.35,129.85）^*
肺癌组	226	93.29（61.74,160.28）^*#
腺癌	148	89.65（59.67,163.56）
鳞癌	51	96.60（65.13,139.99）
其他NSCLC	4	82.03（47.63,142.70）
SCLC	23	102.68（72.74,204.05）

组别	例数	HE4
正常对照组	100	45.64（36.60,62.35）
良性疾病对照组	128	76.47（55.35,129.85）^*
肺癌组	226	93.29（61.74,160.28）^*#
腺癌	148	89.65（59.67,163.56）
鳞癌	51	96.60（65.13,139.99）
其他NSCLC	4	82.03（47.63,142.70）
SCLC	23	102.68（72.74,204.05）

检测指标	AUC（95%可信区间）	cut-off值	敏感性（%）	特异性（%）	约登指数
HE4	0.860（0.818~0.896）	55.137 pmol/L	84.07	72.00	0.561
CEA	0.758（0.708~0.803）	2.51 ng/mL	63.56	76.00	0.396
CYFRA21-1	0.765（0.715~0.810）	3.3 ng/mL	50.88	95.00	0.459
NSE	0.676（0.622~0.726）	14.75 ng/mL	45.58	92.00	0.376
SCC相关抗原	0.610（0.554~0.663）	0.7 ng/mL	46.90	78.00	0.249
LOGREGR_Pred1	0.906（0.868~0.935）	0.641	78.20	88.00	0.660

检测指标	AUC（95%可信区间）	cut-off值	敏感性（%）	特异性（%）	约登指数
HE4	0.860（0.818~0.896）	55.137 pmol/L	84.07	72.00	0.561
CEA	0.758（0.708~0.803）	2.51 ng/mL	63.56	76.00	0.396
CYFRA21-1	0.765（0.715~0.810）	3.3 ng/mL	50.88	95.00	0.459
NSE	0.676（0.622~0.726）	14.75 ng/mL	45.58	92.00	0.376
SCC相关抗原	0.610（0.554~0.663）	0.7 ng/mL	46.90	78.00	0.249
LOGREGR_Pred1	0.906（0.868~0.935）	0.641	78.20	88.00	0.660

组别	例数	HE4
NSCLC组
Ⅰ和Ⅱ期	135	78.74（57.28,113.07）
Ⅲ和Ⅳ期无转移	24	123.26（74.48,189.11）^*
Ⅲ和Ⅳ期有转移	44	196.45（117.06,386.17）^*#
SCLC组
LD	8	71.78（64.69,81.03）
ED	15	146.90（102.68,552.38）^△