目的：探讨云南地区晚期非小细胞肺癌（non-small cell lung cancer，NSCLC）患者外周血中肺癌相关驱动基因突变及其与临床病理特征的关系。方法：收集2019年1月至2019年12月云南省肿瘤医院分子诊断中心检测的304例Ⅳ期NSCLC患者外周血，用二代测序（next generation sequencing, NGS）技术检测NSCLC相关驱动基因突变情况，用卡方检验分析主要突变基因与患者临床病理特征的关系，用Logistic回归分析其独立危险因素。结果：304例Ⅳ期NSCLC患者的外周血中，EGFR基因突变120例（突变率39.47%）、ALK融合12例（3.95%），其他突变如KRAS、BRAF、RET共36例（11.84%）。EGFR突变以19号外显子缺失和 L858R 点突变为主（占总突变的 69.17%），女性、年轻、无吸烟史、无化疗史的肺腺癌患者 EGFR 突变率较高（49.26% vs 31.55%，45.39% vs 33.56%，45.92% vs 27.78%，45.07% vs 26.37%，42.39% vs 10.71%，均P<0.05）。多因素分析结果显示，女性、无化疗史、肺腺癌是EGFR突变的独立危险因素（均P<0.05）。结论：利用NGS技术检测云南地区的晚期NSCLC患者外周血中驱动基因发现女性、无化疗史的肺腺癌患者EGFR突变率更高。

Objective: To investigate the lung cancer-associated driver gene mutations in peripheral blood of patients with advanced non-small cell lung cancer (NSCLC) in Yunnan area, and to explore their association with clinical pathological features. Methods:Peripheral blood of 304 patients with stage Ⅳ NSCLC were collected from Molecular Diagnostic Center of Yunnan Cancer Hospital during January 2019 to December 2019. Next generation sequencing (NGS) technique was used to detect the mutation of NSCLC related driver genes, chi-square test was used to analyze the relationship between the major mutant genes and the clinicopathological features of patients, and Logistic regression was used to analyze the independent risk factors. Results: In the peripheral blood of 304 patients with stage Ⅳ NSCLC, there were 120 (39.47%) cases with EGFR mutations, 12 (3.95%) cases with ALK fusion, 36 (11.84%)case with other mutations such as KRAS, BRAF and RET. The main EGFR mutations were 19del and L858R (69.17%). The mutation rate of EGFR was higher in female, young, non-smoking, non-chemotherapy and lung adenocarcinoma patients (49.26% vs 31.55%,45.39% vs 33.56%, 45.92% vs 27.78%, 45.07% vs 26.37%, 42.39% vs 10.71%, all P<0.05). Multivariate analysis showed that female,no history of chemotherapy and lung adenocarcinoma were independent risk factors for EGFR mutations (all P<0.05). Conclusion:Using NGS technology to detect the driver genes in peripheral blood of patients with advanced NSCLC in Yunnan area showed that the mutation rate of EGFR was higher in women and lung adenocarcinoma patients without chemotherapy history.

国家自然科学基金资助项目（No.8186110513）；云南省科技计划项目资助（No.2017FA037）