非小细胞肺癌组织、血液及胸水EGFR基因突变分析
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摘要
目的探讨非小细胞肺癌(non-small cell lung cancer,NSCLC)患者的EGFR突变情况及血液和胸水标本"液体活检"的可行性。方法收集2015年1月～2017年12月南昌大学第二附属医院确诊为NSCLC患者的肿瘤组织、血液及胸水标本,利用突变扩增系统-聚合酶链式反应(amplification refractory mutation system-polymerase chain reaction,ARMS-PCR)检测EGFR的突变,并分析血液、胸水标本与配对肿瘤组织标本EGFR检测的一致性。结果组织标本EGFR突变率为49. 03%(330/673),突变主要发生于女性、腺癌及低于60岁患者中。与肿瘤组织相匹配的血液、胸水标本检测显示EGFR突变的一致性较好,Kappa值分别为0. 65、0. 82。结论 NSCLC患者EGFR的总突变率为49. 03%,女性、腺癌、低于60岁患者可能是EGFR突变的好发人群;血液、胸水标本中EGFR基因的检测与肿瘤组织标本相比具有较好的一致性;在肿瘤组织缺乏时,可以考虑采用血液、胸水标本进行EGFR基因检测。
Purpose To analyse the mutation of EGFR in patients with non-small cell lung cancer( NSCLC) and to explore the feasibility of "liquid biopsy"based on blood and hydrothorax samples in clinic. Methods Tissue,blood and hydrothorax samples of patients with NSCLC in the Second Affiliated Hospital of Nanchang University from January 2015 to December 2017 were collected. Amplification refractory mutation system-polymerase chain reaction( ARMS-PCR) was used to detect the mutation of EGFR,the consistency of EGFR detection between blood or hydrothorax with matched tumor tissue samples was analysed. Results The mutation rate of EGFR in tissue samples was 49. 03%,the mutation mainly occured in female,adenocarcinoma and less than 60 years old patients. The detection of EGFR mutation in blood and hydrothorax samples matched with tumors showed good consistency with kappa values of 0. 65 and 0. 82,respectively. Conclusion The mutation rate of EGFR in NSCLC patients is 49. 03%. Female,adenocarcinoma and less than 60 years old may be the dominant group of EGFR mutation. The detection of EGFR mutation in blood and hydrothorax samples is in good agreement with that in tumor tissues. In the absence of tumor tissues,blood and hydrothorax can be used to detect EGFR gene.
Purpose To analyse the mutation of EGFR in patients with non-small cell lung cancer( NSCLC) and to explore the feasibility of "liquid biopsy"based on blood and hydrothorax samples in clinic. Methods Tissue,blood and hydrothorax samples of patients with NSCLC in the Second Affiliated Hospital of Nanchang University from January 2015 to December 2017 were collected. Amplification refractory mutation system-polymerase chain reaction( ARMS-PCR) was used to detect the mutation of EGFR,the consistency of EGFR detection between blood or hydrothorax with matched tumor tissue samples was analysed. Results The mutation rate of EGFR in tissue samples was 49. 03%,the mutation mainly occured in female,adenocarcinoma and less than 60 years old patients. The detection of EGFR mutation in blood and hydrothorax samples matched with tumors showed good consistency with kappa values of 0. 65 and 0. 82,respectively. Conclusion The mutation rate of EGFR in NSCLC patients is 49. 03%. Female,adenocarcinoma and less than 60 years old may be the dominant group of EGFR mutation. The detection of EGFR mutation in blood and hydrothorax samples is in good agreement with that in tumor tissues. In the absence of tumor tissues,blood and hydrothorax can be used to detect EGFR gene.
引文
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[13]张仁锋,张岩,温丰标,等.6 058例肺癌患者病理类型和临床流行病学特征的分析[J].中国肺癌杂志,2016,19(3):129-135.
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[15]董丹丹,唐源,邹艳,等.四川地区肺腺癌中EGFR基因19、21外显子突变研究[J].临床与实验病理学杂志,2011,27(12):1306-1309.
[16]张标,杨军.非小细胞肺癌表皮生长因子受体基因突变236例分析[J].江苏大学学报(医学版),2017,27(2):179-182.
[2]Torre L A,Siegel R L,Jemal A.Lung cancer statistics[J].Adv Exp Med Biol,2016,893:1-19.
[3]Gridelli C,Ardizzoni A,Barni S,et al.Medical treatment choices for patients affected by advanced NSCLC in routine clinical practice:results from the Italian observational"SUN"(survey on the lung cancer management)study[J].Lung Cancer,2011,74(3):462-468.
[4]张卉,张树才.非小细胞肺癌EGFR基因靶向治疗研究进展[J].中国肺癌杂志,2017,20(1):61-65.
[5]Soria J C,Ohe Y,Vansteenkiste J,et al.Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer[J].NEngl J Med,2018,378(2):113-125.
[6]朱毅,裴锋.扩增阻滞突变系统检测晚期非小细胞肺癌患者外周血游离DNA中EGFR基因突变[J].中国卫生检验杂志,2016,26(24):3574-3577.
[7]Fassunke J,Ihle M,Lenze D,et al.EGFR T790M mutation testing of non-small cell lung cancer tissue and blood samples artificially spiked with circulating cell-free tumor DNA:results of a round robin trial[J].Virchows Arch,2017,471(4):509-520.
[8]Wang Y,Liu Z,Yin H,et al.Improved detection of EGFR mutations in the tumor cells enriched from the malignant pleural effusion of non-small cell lung cancer patient[J].Gene,2018,644:87-92.
[9]亓岽东,徐建平,朱礼阳,等.EGFR基因突变在非小细胞肺癌胸水细胞块中的检测分析[J].贵州医药,2017,41(1):3-5.
[10]梁颖,林勇平,徐韫健,等.非小细胞肺癌EGFR基因突变的异质性[J].热带医学杂志,2015,15(12):1590-1594.
[11]Goodman A M,Kato S,Bazhenova L,et al.Tumor mutational burden as an independent predictor of response to immunotherapy in diverse cancers[J].Mol Cancer Ther,2017,16(11):2598-2608.
[12]张莹,王哲,杨向红.辽宁沈阳地区非小细胞肺癌EGFR基因突变分析[J].现代肿瘤医学,2018,26(1):35-39.
[13]张仁锋,张岩,温丰标,等.6 058例肺癌患者病理类型和临床流行病学特征的分析[J].中国肺癌杂志,2016,19(3):129-135.
[14]魏丹凤,郭元彪,王战豪,等.四川地区非小细胞肺癌患者EGFR基因突变分型与临床病理特征的相关性分析[J].临床肿瘤学杂志,2018,23(10):915-919.
[15]董丹丹,唐源,邹艳,等.四川地区肺腺癌中EGFR基因19、21外显子突变研究[J].临床与实验病理学杂志,2011,27(12):1306-1309.
[16]张标,杨军.非小细胞肺癌表皮生长因子受体基因突变236例分析[J].江苏大学学报(医学版),2017,27(2):179-182.