循环肿瘤脱氧核糖核酸基因突变检测在非小细胞肺癌中的应用价值

The value of detecting gene mutation in circulating tumor deoxyribonucleic acid in non-small cell lung cancer

目的探讨非小细胞肺癌(NSCLC)患者手术前后组织脱氧核糖核酸(tDNA)和外周血循环肿瘤脱氧核糖核酸(ctDNA)的基因突变情况。方法收集90例原发性NSCLC患者手术切除的肿瘤组织标本及手术前后采集的外周血,采用Ion Proton二代测序平台对表皮生长因子受体外显子(EGFRexon)、TP53、erb-b2受体酪氨酸激酶2(ERBB2)、磷脂酰肌醇3-激酶催化亚基α(PIK3CA)四种基因检测进行测序,分析四种驱动基因的突变情况,比较和分析组织和血浆ctDNA基因突变检测结果的一致性。结果 tDNA和对应的术前血浆ctDNA突变诊断的一致性为75.56%,术前血浆ctDNA突变诊断NSCLC的灵敏度为72.41%,特异度为81.25%,阳性预测值为87.50%。对所有基因突变手术前后的总体平均突变频率进行比较发现,手术前血浆ctDNA的平均突变频率为1.24,手术后血浆ctDNA的平均突变频率为0.13。结论靶向测序检测外周血ctDNA可检出NSCLC患者的突变基因,同时可监测患者的手术治疗效果,对NSCLC患者的早期诊断和治疗具有一定的临床应用价值。

Objective To explore the gene mutation in tissue transferred deoxyribonucleic acid(tDNA)and peripheral blood circulating tumor deoxyribonucleic acid(ctDNA)in patients with non-small cell lung cancer(NSCLC)before and after surgery.Method The surgically resected tumor tissues and peripheral blood collected before and after surgery from 90 patients with primary NSCLC were included in the analysis,epidermal growth factor receptor exon(EGFRexon),TP53,erb-B2 receptor tyrosine kinase 2(ERBB2)and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha(PIK3CA)were detected by Ion Proton second-generation sequencing platform to determine the mutations of the four driving genes,and evaluate the consistency of detecting tissue and plasma ctDNAgene mutations.Result The consistency in diagnosing gene mutation was 75.56%for tDNA and corresponding preoperative plasma ctDNA,the sensitivity of preoperative plasma ctDNA in diagnosing gene mutation was 72.41%,with specificity being 81.25%,and positive predictive value being 87.50%.The overall mean mutation frequency of all gene mutations before and after surgery was compared,and it was found that the average mutation frequency of plasma ctDNA before surgery was 1.24,and the that after surgery was 0.13.Conclusion Targeted sequencing detection of ctDNA in peripheral blood is capable of detecting the gene mutation in non-small cell lung cancer patients,meanwhile,it facilitates the monitoring of surgical effect for patients,and thus is clinically valuable for the early diagnosis and treatment of NSCLC.