目的： 探讨非小细胞肺癌（non-small cell lung cancers，NSCLC）患者表皮生长因子受体（epidermal growth factor receptor, EGFR）信号通路中EGFR、Kirsten鼠肉瘤病毒癌基因(Kirsten rat sarcoma viral oncogene homolog, KRAS)、B-Raf原癌基因丝氨酸/苏氨酸蛋白激酶(B-Raf proto oncogene serine/threonine protein kinase，BRAF)和磷脂酰肌醇-3-激酶α亚单位(phosphatidylinositol -4，5- bisphosphate 3-kinase catalytic subunit alpha，PI3KCA)基因的突变状态及其临床意义，为酪氨酸酶抑制剂（tyrasin kimase inhibitor, TKI)临床用药与科学研究提供依据。方法：采用SurPlex-xTAG70plex液相芯片技术平台检测中国430例NSCLC患者的福尔马林固定石蜡包埋(formalin fixed paraffin embedded, FFPE)组织中EGFR、KRAS、BRAF和PIK3CA基因的突变状态，分析基因的突变率及其与临床病理特征的关系。结果： EGFR、KRAS、BRAF和PIK3CA的突变率分别为41.2%，79%，0.7%和3.7%。EGFR外显子19、21在女性患者中的突变率明显高于男性（P<0.01）, 在肺腺癌患者中的突变率明显高于其他类型肺癌（P<0.01），在无吸烟史患者中的突变率高于有吸烟史的患者（P<0.01）。相反地，KRAS突变在男性患者中的突变率高于女性（P<0.05），在肺腺癌中的突变率高于肺鳞癌（P<0.005），有吸烟史患者的突变率高于无吸烟史患者（P<0.01）。在肺腺癌患者中PIK3CA的突变率明显低于其他类型肺癌（P<0.01）。结论： EGFR和KRAS基因突变率与性别、组织学类型及吸烟史密切相关。在检测中发现EGFR和KRAS双突变，此外PIK3CA突变并非与EGFR和KRAS突变互斥。

Objective:To provide guide for the clinical medication of EGFR-tyrosine kinase inhibitors (TKIs) and discussion of their association with clinical pathological features, we investigated the amplification and mutation status of genes encoding epidermal growth factor receptor (EGFR), Kirsten rat sarcoma viral oncogene homolog (KRAS), B-Raf proto oncogene serine/threonine protein kinase (BRAF) and phosphatidylinositol -4，5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) in NSCLC patients.Methods:EGFR, KRAS, BRAF and PIK3CA mutations in 430 randomly selected Chinese patients with NSCLC were analyzed by SurPlex-xTAG70plex platform. The relationship between the mutations and the clinicopathologic features was further evaluated.Results: The mutation rates of EGFR, KRAS, BRAF and PIK3CA were 41.2%, 7.9%, 0.7%, and 3.7% respectively in these patients. The mutation rates of EGFR exon 19 and 21 were higher in females than those in males (P<0.01), significantly increased in adenocarcinomas compared to those in the other forms of lung cancers (P<0.01), and risen markedly in non-smokers compared to those in smokers (P<001). Conversely, the KRAS mutation rates were higher in males than those in females (P<0.05), increased significantly in adenocarcinomas compared to those in the other forms of lung cancers (P<0.005), and risen markedly in smokers compared to those in non-smokers (P<0.01). The PIK3CA mutation rates were significantly lower in adenocarcinomas compared to those in the other forms of lung cancers (P<0.01). Conclusion: The mutation rates of EGFR and KRAS in NSCLC are associated with gender, pathohistology, and smoking habits. Concurrent presence of EGFR and KRAS mutations was found in NSCLC from these patients, and the mutational statuses of PIK3CA and EGFR or KRAS were not mutually exclusive.

广东省科学技术厅“高新区及孵化育成体系建设领域”专项资助（No. 2014B010108005)