血清肿瘤标志物HE4检测在肺癌诊断中的应用价值探讨

Investigation on the application significance of serum tumor biomarker HE4 detection in the diagnosis of lung cancer

目的探讨肿瘤标志物人附睾蛋白4(HE4)在肺癌患者组织及血清中的表达水平及其在肺癌鉴别诊断中的价值。方法对肺腺癌、鳞癌、癌旁组织切片进行免疫组化测定;采用酶联免疫吸附试验(ELISA)对214例肺癌患者及76名正常人进行血清HE4水平检测,同时检测鳞状上皮细胞癌抗原(SCC)、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),各组之间进行比较分析。结果免疫组化结果显示,HE4在肺腺癌组织切片阳性程度高于鳞癌,在癌旁组织上基本不表达;肺癌组患者血清HE4水平为85.04(64.91,118.40)pmol/L,显著高于正常对照组[48.48(43.12,58.81)pmol/L,P<0.01]。HE4、CYFRA21-1以及CEA通过受试者工作特征(ROC)曲线进行对比后发现,HE4检测非小细胞肺癌的诊断效率优于CYFRA21-1和CEA。在联合检测中,常用的肺癌4项检测(SCC、CEA、CYFRA21-1、NSE)对肺癌的检出阳性率为79.44%,而HE4参与的联合检测阳性率显著提升为89.72%。在肺腺癌的诊断中,CEA和CYFRA21-1联合检测的检出阳性率为68.46%,而HE4参与的联合检测阳性率为82.31%。结论 HE4可作为肺癌的血清学标志物,是肺癌早期辅助诊断的有用指标。

Objective To investigate the expression level of tumor biomarker human epididymis protein 4( HE4)in tissue and serum of patients with lung cancer and its role in differential diagnosis of lung cancer. Methods HE4 expressions in lung adenocarcinoma,lung squamous cell carcinoma and cancer-adjacent tissues were detected by immunohistochemistry,and serum HE4 levels were determined in 214 patients with lung cancer and 76 healthy subjects by enzyme-linked immunobsorbent assay( ELISA). Simultaneously,the serum levels of squamous cell carcinoma antigen( SCC),carcinoembryonic antigen( CEA),cytokeratin 19 fragment( CYFRA21-1) and neuron-specific enolase( NSE) were determined. The results were compared and analyzed among the groups. Results Lung adenocarcinoma tissues showed stronger positive staining than lung squamous cell carcinoma tissues,and the negative staining was shown in cancer-adjacent tissues. The level of serum HE4 in lung cancer patients[85. 04( 64. 91,118. 40) pmol /L] was significantly higher than that of healthy controls [48. 48( 43. 12,58. 81) pmol /L,P < 0. 01]. HE4 had a better diagnosis efficiency than CYFRA21-1 and CEA in non-small cell lung cancer through receiver operating characteristic( ROC) curve analysis. The positive rate of combined detection of SCC,CEA,CYFRA21-1 and NSE was 79.44% for lung cancer. However,HE4 improved the positive rate to 89. 72% when combined with this biomarker panel. In the diagnosis of lung adenocarcinoma,the positive rate of combined detection of CEA and CYFRA21-1 was 68. 46%.Moreover,HE4 improved the positive rate to 82. 31% when combined with this biomarker panel. Conclusions HE4,as a biomarker of lung cancer,is a useful indicator for the early diagnosis of lung cancer.