非小细胞肺癌患者外周血中BJ—TSA-9、CK19、Pre-proGRP mRNA的表达及联合检测的意义  

Clinical significance of expressions of tumor markers in peripheral blood in non-small cell lung cancer

作　　者：曲怡梅[1] 廖国清[1] 刘鹏辉[1] 王红梅[1] 刘蕾[2] 李亮亮[1] 解国清[1] 

机构地区：[1]解放军第三0九医院肿瘤科,北京100091 [2]北京大学医学部免疫系

出　　处：《中华医学杂志》2010年第28期1958-1962,共5页National Medical Journal of China

基　　金：国家自然科学基金（30772500）

摘　　要：目的研究非小细胞肺癌（NSCLC）患者外周血中肿瘤特异性抗原9（BJ-TSA-9）、细胞角蛋白19（CKl9）、胃泌素释放肽前体（Pre-proGRP）mRNA的表达及其联合检测的临床意义。方法选取2006年1月至2007年3月解放军第三0九医院收治的120例NSCLC患者、106例肺良性疾病患者及80名健康志愿者，采用巢式PCR技术检测外周血BJ-TSA-9、CKl9、Pre-proGRP mRNA的表达；结合NSCLC患者的病理结果、肿瘤类型、临床分期对检测结果的敏感度、特异度进行统计学分析，绘制ROC曲线；同时分析此3项指标与患者预后的相关性。结果BJ—TSA-9、CK19、Pre-proGRP mRNA在NSCLC患者中的表达阳性率分别为56．7％、57．5％、35．0％，明显高于肺良性病变组（0．9％、6．6％、5．7％）和健康对照组（0、3．8％、0，均P〈0．05）。ROC曲线提示联合检测3个基因的敏感度为84．3％，特异度为94．6％。单因素分析提示疾病分期、东方协作肿瘤组织（ECOG）体力状态评分、3个基因表达的个数与总生存期相关（X^2=67．928、95．981、60．285，均P=0．000）。多因素分析提示疾病分期、ECOG评分、3个基因表达个数是独立预后指标（HR=2．866、4．251、1．845，均P=0．000）。结论BJ-TSA-9、CKl9、Pre-proGRP mRNA可作为检测NSCLC患者外周血微转移的标记物，联合检测有助于提高准确性。Objective To investigate the expressions of BJ-TSA-9, CK19 and Pre-proGRP mRNA in peripheral blood from the patients with non-small cell lung cancer and analyze their correlations with non- small cell lung cancer. Methods The expressions of BJ-TSA-9, CK19 and Pre-proGRP mRNA were detected by nested reverse transcription-PCR assay in peripheral blood from the patients with non-small cell lung cancer（ n = 120 ）, benign pulmonary disease （ n = 106 ） and from healthy subjects （ n = 80 ） so as to further investigate their relationship with clinicopathological features and prognosis. Meantime we also examined the sensitivity, specificity and accuracy of combination detection. Results The expressions of BJ- TSA-9, CK19 and Pre-proGRP mRNA in non-small cell lung cancer patients were 56. 7% ,57. 5% ,35.0% , higher than that of benign pulmonary disease （ 0. 9%, 6. 6%, 5.7% ） and healthy groups （ 0,3.8% , 0, all P 〈 0. 05 ）. The ROC curves indicated the sensitivity of combined detection was 84. 3 % and the specificity of combined detection was 94. 6%. Univariate analysis revealed that the clinical stage,the ECOG score and the number of positive marker had significant association with overall survival （ OS ） （ X^2 = 67. 928, 95. 981, 60. 285, all P = 0. 000）. Multivariate analysis indicated that the clinical stage, ECOG score and the number of positive marker was an independent prognostic factor each （ HR = 2. 866,4. 251,1. 845, all P = 0. 000 ）. Conclusion BJ-TSA-9, CK19 and Pre-proGRP mRNA may be the specific and sensitive markers to detect circulating tumor cells in the peripheral blood of non-small cell lung cancer patients.

关 键 词：癌 非小细胞肺 聚合酶链反应 角蛋白质类 胃泌素释放肽 

分 类 号：R734.2[医药卫生—肿瘤]