目的：探讨多结节非小细胞肺癌（NSCLC）组织中的驱动基因突变情况与临床病理特征的关系，为多结节NSCLC患者治疗提供分子诊断依据。方法：本研究共纳入2018 年1月至2023 年10 月间云南省肿瘤医院分子诊断中心检测的121 例多结节NSCLC患者的253个肺结节肿瘤组织标本，以第二代测序（NGS）技术或扩增阻滞突变系统PCR（ARMS-PCR）技术检测多结节NSCLC 组织中驱动基因突变情况，分析其与患者临床病理特征的关系，比较不同结节间肺癌驱动基因的突变异质性。结果：与非“宣威”NSCLC 相比，“宣威”多结节NSCLC 患者驱动基因突变具有显著的地域特点，表现在“宣威”患者具有较低（20%）的EGFR 敏感突变（L858R、19-del）及较高（27.26%）的EGFR 少见突变（主要为G719/S768I、G719）；“宣威”多结节NSCLC 患者的KRAS 突变率（27.27%）亦显著高于非“宣威”患者突变率（12.59%）（P<0.05）。此外，“宣威”多结节NSCLC 患者驱动基因突变不一致率高达69.23%，远高于非“宣威”患者驱动基因突变不一致率（55.07%）（P<0.05）。结论：“宣威”多结节NSCLC 患者具有较高的EGFR 少见突变及KRAS 突变率，同一患者不同病灶之间存在更高的驱动基因突变异质性，本研究将为“宣威”多结节NSCLC的诊疗策略提供更多的选择。

Objective: To investigate the relationship between driver gene mutations and clinicopathological features of multi-nodular non-small cell lung cancer (NSCLC)，and to provide molecular diagnostic basis for the treatment of multi-nodular NSCLC patients. Methods: A total of 253 lung nodule tumor specimens from 121 patients with multiple nodules NSCLC tested at the Molecular Diagnostic Center of Yunnan Cancer Hospital between January 2018 and October 2023 were included in this study. Next-generation sequencing (NGS) or Amplification Refractory Mutation System PCR (ARMS-PCR) techniques were used to detect driver gene mutations in multi-nodular NSCLC tissues. The relationship between these mutations and clinical pathological features of patients was analyzed, in order to compare the tumor heterogeneity of lung cancer driver genes in different nodules. Results: Compared with non-"Xuanwei" NSCLC, "Xuanwei" multi-nodular NSCLC patients showed significant regional characteristics in driver gene mutations. These patients demonstrated a lower rate (20%) of epidermal growth factor receptor (EGFR) sensitive mutations (L858R, 19-del), a higher rate (27.26%) of EGFR rare mutations (mainly G719/S768I, G719). The KRAS mutation rate in "Xuanwei" multi-nodular NSCLC patients (27.27%) was also significantly higher than that in non- "Xuanwei" patients (12.59%) (P<0.05). In addition, the inconsistency rate of driver gene mutations among different nodules was 69.23% in "Xuanwei" multi-nodular NSCLC patients, much higher than that in non-"Xuanwei" patients (55.07%) (P<0.05). Conclusion: "Xuanwei" multi-nodular NSCLC patients in have higher EGFR rare mutations and KRAS mutation rates, and there is higher driver gene mutation heterogeneity among different lesions in the same patient. This study will provide more options for the diagnosis and treatment strategies of "Xuanwei" multi-nodular NSCLC.

云南省教育厅科学研究基金项目（No. 2023J0276）；云南省科技厅-昆明医科大学联合专项（No. 202001AY070001-150）；云南省肺癌研究重点实验室项目（No. CZ0049）