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

Abstract

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200/年3月解放军第三○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(x2=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、CK19、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-preGRP mRNA in peripheral blood from the patients with non-small cell lung cancer and analyze their correlations with nonsmall 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 BJTSA-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) ( x2 = 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.