云南地区多结节肺腺癌EGFR突变及其临床意义

目的 探讨使用下一代测序(Next-generation sequencing,NGS)技术检测云南地区多结节肺腺癌患者肿瘤组织中EGFR基因突变与临床病理特征的关系。方法 收集2018年1月至2020年5月云南省分子诊断中心共检测的79例多结节肺腺癌患者送检的111枚肺结节肿瘤组织样本,以NGS法检测EGFR突变情况分析其与临床病理特征的关系,Logistic回归分析其独立危险因素。结果 111枚肺结节组织样本中EGFR总突变率58.55%(65/111),其中L858R点突变和19号外显子缺失最常见,占总突变的53.8%(35/65)。稀有突变率27.02%(30/111),单点突变率37.84%(42/111),复合突变率20.72%(23/111)。χ²检验显示女性、年龄≥56岁、无吸烟史、云南区域性高发肺癌地区患者EGFR基因突变率较高,差异具有统计学意义(P=0.024、P=0.008、P <0.001、P=0.024)。Logistic回归分析显示：年龄≥56岁、无吸烟史、云南区域性高发肺癌地区是EGFR基因突变的独立危险因素(P <0....

EGFR Gene Mutation State and Its Clinical Significance in Multi-nodular Lung Adenocarcinoma in Yunnan Province

  Objective  To investigate the relationship between EGFR gene mutations and clinicopathological characteristics of patients with multinodular lung adenocarcinoma in Yunnan province by using NGS method.   Methods  A total of 111 pulmonary nodule samples from 79 patients with multifocal lung adenocarcinoma were collected between January 2018 to May 2020 in the Molecular Diagnostic Center of Yunnan Cancer Hospital. The NGS method was used to detect the EGFR mutation of multiple lung nodules to analyze its relationship with clinicopathological characteristics, and Logistic regression to analyze its independent risk factors.   Results  The total EGFR mutation rate in 111 lung nodule tissue samples was 58.55% （65/111）, among which L858R point mutation and exon 19 deletion were the most common, accounting for 53.8%of the total mutations （35/65）.The rare mutation rate was 27.02% （30/111）, the single point mutation rate was 37.84% （42/111）, and the compound mutation rate was 20.72% （23/111）. χ2 test showed that females, age ≥56 years, non-smoker, areas with a high incidence of lung cancer in Yunnan, earlier pathological stages （stages Ⅰ to Ⅱ）, and invasive adenocarcinoma had a higher EGFR gene mutation rate, and the difference was statistically significant （P = 0.036、P = 0.001、P < 0.001、P = 0.006、P = 0.006、P = 0.034）.Multivariate Logistic regression analysis showed thatage ≥56 years, non-smoker, areas with a high incidence of lung cancer in Yunnan, and earlier pathological stages （stages Ⅰ to Ⅱ） are independent risk factors for EGFR gene mutations （P＜0.05）.The heterogeneity rate of EGFR gene expression between paired nodules in the same patient was as high as 87.5% （28/32）.  Conclusions  Among patients with multinodular lung adenocarcinoma in Yunnan, the elderly, non-smoker, areas with a high incidence of lung cancer in Yunnan, and earlier pathological stages （stages Ⅰ to Ⅱ） are independent risk factors for EGFR gene mutations.The high-level heterogeneity of driver mutations among the lesions of patients with multinodular lung adenocarcinoma suggests that multiple nodules tend to be independent of the origin of the primary tumor, which will provide more options for the diagnosis and treatment of multinodular lung adenocarcinoma.