[细胞角蛋白19信使核糖核酸、癌胚抗原、神经元特异性烯醇化酶及组织多肽抗原联合检测在肺癌患者外周血中的意义]

[Significance of combined determination of CK19mRNA, carcinoembryanic antigen, neuron-specific enolase, and tissue polypeptide antigen in peripheral blood of patients with lung cancer].

作者信息

Pan Qiang-rong, Zhang Xing, Xu Ze-feng, Zheng Shu

机构信息

Clinical Experimental Research Center, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, P. R. China.

出版信息

Ai Zheng. 2002 Feb;21(2):196-9.

DOI:

PMID:12479076

Abstract

BACKGROUND & OBJECTIVE: Cellular keratin, an indicator for cancer cell in circulation gains increasing attention. Although CK19mRNA as a gene marker used to identify micro-metastasis is of relatively high practical value, it lacks specificity and sensitivity in diagnosis of cancer. The aim of this study is to evaluate whether the combined detection of CK19mRNA with other tumor markers, such as carcinoembryanic antigen(CEA), neuron-specific Enolase(NSE), tissue polypeptide antigen(TPA), would improve the diagnosis of lung cancer.

METHODS

The expression level of CK19mRNA in peripheral blood mononucleated cells (PBMCS) was determined by RT-PCR, The levels of CEA, NSE, and TPA in serum were determined by enzyme-linked immunosorbent assay (ELISA) and time-resolved fluorometry(TRF) in 91 patients with lung cancer, 33 with benign lung diseases (BLD) and 50 healthy controls. The data was analyzed by t test and chi 2 test.

RESULTS

The positive rates of CK19mRNA, CEA, NSE, and TPA in lung cancer group (49.5%, 65.9%, 67.0%, and 83.5%, respectively) were remarkably higher than in BLD group(24.2%, 9.0%, 15.2%, and 9.0%, respectively) and in healthy control group (10.0%, 4.0%, 8.0%, and 6.0%, respectively) (P < 0.01). The positive rate of CK19mRNA was not statistically different in various histological subtypes (P > 0.05). Although the positive rate of CK19mRNA appeared to be associated with the clinical stage (stage I + II: 44.4%, stage III: 48.4%, stag IV: 54.2%), there was no statistical significance among the three groups (P > 0.05). The serum level (microgram/L)/positive rate of CEA(3.5/27.8%, 5.1/35.5%, and 8.5/58.3%, respectively), NSE (12.5/33.3%, 15.3/41.9%, and 24.7/58.3%, respectively), and TPA (1.1/44.4%, 1.8/58.1%, and 3.6/66.7%, respectively) in stage I + II, III, and IV appeared to be associated with the clinical stages of lung cancer, but no statistical significance among the three groups (P > 0.05). Combined detection of three or four tumor markers yielded significant higher effective accuracy in diagnosis of lung cancer than that of any of two tumor markers or single tumor marker (P < 0.05). In addition, the results showed that TPA, CEA, and NSE were relatively specific for squamous cell carcinoma (76.7%), adenocarcinomas (83.3%), and small-cell lung cancer (79.2%), respectively.

CONCLUSION

The combined measurement of CK19mRNA with CEA, NSE, and TPA can increase diagnosis rate of lung cancer, can also provide potent diagnosis basis for treatment.

摘要

背景与目的

循环肿瘤细胞角蛋白作为一种循环癌细胞的指标，越来越受到关注。虽然CK19mRNA作为一种用于识别微转移的基因标志物具有较高的实用价值，但在癌症诊断中缺乏特异性和敏感性。本研究旨在评估CK19mRNA与其他肿瘤标志物，如癌胚抗原（CEA）、神经元特异性烯醇化酶（NSE）、组织多肽抗原（TPA）联合检测是否能提高肺癌的诊断率。

方法

采用逆转录聚合酶链反应（RT-PCR）检测91例肺癌患者、33例良性肺疾病（BLD）患者和50例健康对照者外周血单个核细胞（PBMCS）中CK19mRNA的表达水平，采用酶联免疫吸附试验（ELISA）和时间分辨荧光免疫分析（TRF）检测血清中CEA、NSE和TPA的水平。数据采用t检验和卡方检验进行分析。

结果

肺癌组CK19mRNA、CEA、NSE和TPA的阳性率（分别为49.5%、65.9%、67.0%和83.5%）显著高于BLD组（分别为24.2%、9.0%、15.2%和9.0%）和健康对照组（分别为10.0%、4.0%、8.0%和6.0%）（P<0.01）。CK19mRNA在不同组织学亚型中的阳性率差异无统计学意义（P>0.05）。虽然CK19mRNA的阳性率似乎与临床分期有关（Ⅰ+Ⅱ期：44.4%，Ⅲ期：48.4%，Ⅳ期：54.2%），但三组之间差异无统计学意义（P>0.05）。CEA（分别为3.5/27.8%、5.1/35.5%和8.5/58.3%）、NSE（分别为12.5/33.3%、15.3/41.9%和24.7/58.3%）和TPA（分别为1.1/44.4%、1.8/58.1%和3.6/66.7%）在Ⅰ+Ⅱ期、Ⅲ期和Ⅳ期的血清水平/阳性率似乎与肺癌的临床分期有关，但三组之间差异无统计学意义（P>0.05）。联合检测三种或四种肿瘤标志物在肺癌诊断中的有效准确率显著高于任何两种肿瘤标志物或单一肿瘤标志物（P<0.05）。此外，结果显示TPA、CEA和NSE分别对鳞状细胞癌（76.7%）、腺癌（83.3%）和小细胞肺癌（79.2%）具有相对特异性。