目的：探索肺癌患者伴随基因突变/扩增频数的变化，并分析其临床意义。方法：回顾性分析苏州大学附属第二医院2015年12月至2020年7月经新一代基因测序（next-generation sequencing technology, NGS）检测的71例（132份肺癌患者标本基因检测数据，其中包括血液标本67份、肿瘤组织48份、胸腔积液15份、脑脊液2份，采用Graphpad prism7.0统计软件统计分析不同临床标本伴随基因状态。结果：所有检测标本除表皮生长因子受体（epidermal growth factor receptor，EGFR）突变之外，另可检测到前5位基因突变/扩增分别为肿瘤蛋白p53（tumor suppressor protein p53，TP53）、鼠类肉瘤病毒癌基因（kirsten rat sarcoma viral oncogene，KRAS）、表皮生长因子受体2（human epithelial growth factor receptor 2，ERBB2）、视网膜母细胞瘤基因1（Retinoblastoma1，RB1）、肝细胞生长因子酪氨酸激酶受体（hepatocyte growth factor receptor，MET）。初诊肺癌患者血液标本共入组50例，EGFR突变阳性率34%（17/50），除EGFR突变之外，所检测标本另外还可检测到79种基因突变/扩增，所有标本共出现123次伴随基因突变/扩增频数，平均2.46次/例，血液标本伴随基因突变／扩增频数与患者临床分期、吸烟、年龄、性别、病理类型均无关（均P＞0.05）。初诊肺癌患者肿瘤组织共入组46例，EGFR突变阳性率50%（23/46），除EGFR突变之外，所检测标本另外还可检测到160种基因突变/扩增，所有标本共出现285次伴随基因突变／扩增频数，平均6.20次/例，肿瘤组织伴随基因突变／扩增频数与患者临床分期、年龄均无关（均P＞0.05），与吸烟、性别、病理类型均有关（U=74.000，P＜0.001；U=130.5，P=0.003；F=8.968，P=0.011)。亚组分析发现，血液标本及肿瘤组织中TP53是否突变对患者生存率影响无统计学差异（血液标本: x2=0.321，P=0.571;肿瘤组织：x2=0.309，P=0.579）。对同时进行肿瘤组织和血液标本配对检测的患者，初诊肿瘤组织伴随基因突变／扩增频数[3（1，8）]高于同一患者的血液标本[3（0，1）]，差异有统计学意义（W=-150，P=0.001）。动态监测抗肿瘤治疗前后的17例患者，抗肿瘤治疗前及抗肿瘤治疗后两组伴随基因突变／扩增频数相比（[1（0，2）]，[1（0，3）]），差异无统计学意义（W=-3，P=0.916）。结论：肺癌患者抗肿瘤治疗前即存在多种伴随基因突变／扩增，有吸烟史、男性患者具有较高水平的伴随基因突变/扩增频数，伴随基因突变／扩增频数的改变不能提示患者病情进展，TP53突变与否对患者生存率无显著影响。
Objective: To observe the changes of the concomitant gene mutation/amplification in patients with lung cancer based on next generation sequencing (NGS) technology and analyze its clinical significance. Methods: Retrospective analysis was performed on 71 lung cancer patients (132 samples) detected by NGS technology in the Second Affiliated Hospital of Soochow University from December 2015 to July 2020, including 67 blood samples, 48 tumor tissues, 15 pleural effusion and 2 cerebrospinal fluid. GraphPad prism7.0 statistical software was used for statistical analysis of concomitant gene mutation/amplification in different clinical samples. Results: In addition to EGFR mutation, mutations/amplification of the first 5 genes were: TP53, KRAS, ERBB2, RB1 and MET. A total of 50 newly diagnosed patients' blood samples were detected by NGS technology. The results showed that EGFR positive rate was 34% (17/50). Except EGFR mutation, there were 79 kinds of gene mutations/amplifications detected, with an average of 2.46 times/example. But with no statistical difference in concomitant gene mutation/amplification among clinical stage, smoking status, age, gender and pathological classification groups in blood samples. A total of 46 newly diagnosed patients' tissue samples were detected by NGS technology. Of which EGFR positive rate was 50% (23/46). Except EGFR mutation, there were 160 kinds of gene mutations/amplifications detected, with an average of 6.20 times/example. There was no statistical difference in concomitant gene mutation/amplification between clinical stage and age groups in tissue samples（P＞0.05）. But in terms of smoking status, gender and pathological classification groups, we could find statistically difference (U=74.000，P＜0.001；U=130.5，P=0.003；F=8.968，P=0.011）. At the same time, TP53 mutation or not had no statistical significance on percent survival（the blood group: x2=0.321，P=0.571; the tissue group：x2=0.309，P=0.579）. For the same patient, the frequency of gene mutation/amplification in the tissue group（[3（1，8）]）was higher than that in the blood group [3（0，1）] of the same patient, and the difference was statistically significant (W=-150，P =0.001). In the 17 patients with dynamic monitoring, there was no statistically significant difference in the frequency of concomitant gene mutation/amplification between the two groups before and after anti-tumor treatment(W=-3，P=0.916). Conclusion: There may be multiple parallel gene mutations/amplifications before the first-line treatment for lung cancer. Previous smoking and male patients were associated with higher levels of mutation/amplification status. Changes in the frequency of gene mutation/amplification cannot indicate disease progression, and TP53 mutation has no significant effect on the percent survival of patients.