基于二代测序的肺癌患者外周血ctDNA突变与临床病理特征的相关性研究

Correlation between ctDNA mutation and clinicopathological features of peripheral blood in patients with lung cancer based on next-generation sequencing

目的 基于二代测序(NGS)技术对肺癌患者外周血游离表皮生长因子受体(EGFR)、鼠类肉瘤病毒癌基因(KRAS)、人第10号染色体缺失的磷酸酶(PTEN)、MNNG HOS转化基因(MET)、磷脂酰肌醇激酶催化亚基α多肽基因(PIK3CA)及人抑癌基因TP53(T P53)基因的突变情况进行检测,分析其与临床病理特征的相关性,以期协助肺癌的临床诊疗.方法 前瞻性纳入2017年12月至2018年7月就诊于空军军医大学唐都医院的194例肺癌患者,采用NGS检测受试者血液样本中游离EGFR、KRAS、PTEN、MET、PIK3CA及TP53基因的突变情况,初步探讨基因突变与临床病理特征之间的相关性及危险因素,并进一步分析各基因之间的关系.结果 EGFR在女性(P=0.007)、不吸烟(P=0.034)的肺癌患者中的突变率明显升高;KRAS突变与肿瘤转移显著相关(P=0.029);PTEN、MET、PIK3CA突变与临床病理特征之间均无相关性(P值均>0.05);T P53突变与病理类型显著相关(P=0.001).性别与吸烟史是EGFR突变的危险因素(P=0.007、0.035),病理类型是TP53突变的危险因素.EGFR与PIK3CA之间有相关性(P=0.005);KRAS与PTEN、MET、PIK3CA、TP53之间均显著相关(P值均<0.05);MET与PIK3CA有相关性(P=0.007),但与TP53之间无相关性(P=0.246);PIK3CA与TP53之间无相关性(P=0.075).结论 基于NGS技术可密切监测肺癌患者外周血基因突变谱的改变,对精确个体化治疗具有良好的临床应用价值.

Objective Based on the next-generation sequencing ( NGS) detection technique , the mutations of free epidermal growth factor receptor (EGFR) ,kirsten rat sarcoma viral oncogene ( KRAS) ,phosphatase and tensin homolog deleted on chromosome ten ( PTEN ) ,MNNG HOS transforming gene ( MET ) ,phosphatidylinositol-4 ,5-bisphosphonate 3-kinase ,catalytic subunit , alpha polypeptide gene ( PIK3CA) and tumor protein TP53 ( TP53) genes in peripheral blood of patients with lung cancer ,and the correlation with clinicopathological features was analyzed to assist Clinical diagnosis and treatment of lung cancer .Methods Prospectively included 194 patients with lung cancer who were admitted to Tangdu Hospital ,Air Force Military Medical University from December 2017 to July 2018 .NGS technology was used to detect the mutations of free EGFR , KRAS ,PTEN ,MET ,PIK3CA and TP53 genes in blood samples .The relationship between genetic mutations and clinicopathological features and risk factors were explored ,and the relationship between genes was further analyzed .Results The mutation rate of EGFR in lung cancer patients with female ( P = 0 .007 ) and non-smoking ( P = 0 .034 ) was significantly increased;KRAS mutation was significantly associated with tumor metastasis ( P =0 .029);There was no correlation between PTEN ,MET ,PIK3CA mutation and clinicopathological features ( all P > 0 .05);TP53 mutation was significantly correlated with pathological type ( P = 0 .001 ) .Gender and smoking history were risk factors for EGFR mutations ( P =0 .007 ,0 .035) ,and pathological types were risk factors for TP53 mutations .There was a correlation between EGFR and PIK 3CA ( P = 0 .005);KRAS was significantly correlated with PTEN ,MET ,PIK3CA ,TP53 (all P <0 .05);There was a correlation between MET and PIK3CA( P =0 .007) ,but there was no significant correlation with TP53 ( P =0 .246);there was no significant correlation between PIK3CA and TP53( P =0 .075) . Conclusions Based on the NGS technology ,the changes of gene mutation spectrum in peripheral blood of patients with lung cancer can be closely monitored ,which has good clinical application value for precise individualized treatment .