食管鳞癌组织中EGFR、KRAS及PIK3CA基因突变的检测及其临床意义分析

Detection of EGFR, KRAS and PIK3CA gene mutations in esophageal squamous cell carcinoma and analysis of their clinical significance

目的分析食管鳞癌组织中表皮生长因子受体(EGFR)、Kirsten鼠类肉瘤病毒癌基因(KRAS)和磷脂酰肌醇3激酶(PIK3CA)基因的突变情况及其与患者临床特征的关系。方法选取2006年1月至2012年12月在新疆医科大学第一附属医院确诊的210例食管鳞癌患者的组织标本进行DNA提取和目标位点扩增,再利用一代测序的方法对EGFR18号和21号外显子、KRAS2号外显子、PIK3CA9号外显子进行测序,探讨各基因突变情况及其与临床病理特征的关系,并分析不同基因突变之间的相关性。结果210例食管鳞癌标本中EGFR基因突变率为27.14%,KRAS基因突变率为14.29%,PIK3CA基因突变率为18.59%,EGFR和KRAS双基因联合突变率为4.76%,EGFR和PIK3CA双基因联合突变率为5.71%,EGFR、KRAS、PIK3CA三基因联合突变率为1.43%。EGFR基因突变与性别、肿瘤直径、分化程度具有相关性(P<0.05),KRAS基因突变与肿瘤直径、分化程度、T分期、临床分期具有相关性(P<0.05),PIK3CA基因突变与性别、肿瘤直径、分化程度具有相关性(P<0.05),EGFR和PIK3CA联合突变与性别、肿瘤直径、分化程度具有相关性(P<0.05)。EGFR基因突变与KRAS基因突变具有相关性(P<0.05),而EGFR基因突变与PIK3CA基因突变之间无相关性(P>0.05)。结论食管鳞癌组织中EGFR基因突变率最高,PIK3CA基因突变率次之,KRAS基因突变率最低;EGFR与KRAS或PIK3CA基因突变联合检测具有一定的临床意义。

Objective To analyze the mutations of epidermal growth factor receptor(EGFR),kirsten ratsarcoma viral oncogene(KRAS),phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha(PIK3CA)gene in esophageal squamous cell carcinoma(ESCC)tissue and their relationship with clinical characteristics.Method DNA extraction and target site amplification were performed on tissue samples from 210 esophageal squamous cell carcinoma patients diagnosed at the First Affiliated Hospital of Xinjiang Medical University from January 2006 to December 2012.Then,first generation sequencing was used to sequence EGFR exons 18 and 21,KRAS exon 2,and PIK3CA exon 9.The mutation status of each gene and its relationship with clinical and pathological characteristics were analyzed,and the correlation between different gene mutations was also analyzed.Result The mutation rate of EGFR gene,KRAS gene and PIK3CA gene in 210 ESCC samples was 27.14%,14.29%and 18.59%respectively;The combined mutation rate of EGFR and KRAS was 4.76%,the combined mutation rate of EGFR and PIK3CA was 5.71%,and the combined mutation rate of EGFR,KRAS and PIK3CA was 1.43%;EGFR gene mutation was related to gender,tumor diameter and degree of differentiation(P<0.05),KRAS gene mutation was related to tumor diameter,degree of differentiation,T stage and clinical stage(P<0.05),and PIK3CA gene mutation rate was related to gender,tumor diameter and degree of differentiation(P<0.05);The combined mutation rate of EGFR and PIK3CA genes was related to sex,tumor diameter and differentiation degree(P<0.05).And there is correlation between EGFR gene and KRAS gene mutation(P<0.05),while there is no correlation between EGFR gene and PIK3CA gene mutations(P>0.05).Conclusion The mutation rate of EGFR gene is the highest in ESCC,the mutation rate of PIK3CA gene is the second,and the mutation rate of KRAS gene is the lowest.The combined mutation of EGFR and KRAS gene or EGFR and PIK3CA gene has certain clinical significance.