临床ⅠA期肺腺癌的基因突变特征及其与患者长期预后的关系  

Gene mutation characteristics of clinical stageⅠA lung adenocarcinoma and their relations with patients′long-term prognosis

作　　者：张丽 刘梦雯 李琳 赵爽 吴丽虹 尹朝华 李蒙 高燕宁 吴宁 Zhang Li;Liu Mengwen;Li Lin;Zhao Shuang;Wu Lihong;Yin Zhaohua;Li Meng;Gao Yanning;Wu Ning(Department of Diagnostic Radiology,National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100021,China;Department of Pathology,National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100021,China;Pediatric Translational Medicine Institute,Shanghai Children's Medical Center,School of Medicine,Shanghai Jiao Tong University,Shanghai 200127,China;DeepKinase Technology Co.Ltd.,Beijing 102206,China;State Key Laboratory of Molecular Oncology,Department of Etiology and Carcinogenesis,National Cancer Center/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100021,China)

机构地区：[1]国家癌症中心、国家肿瘤临床医学研究、中心中国医学科学院北京协和医学院肿瘤医院影像诊断科,北京100021 [2]国家癌症中心、国家肿瘤临床医学研究中心、中国医学科学院北京协和医学院肿瘤医院病理科,北京100021 [3]上海交通大学医学院附属上海儿童医学中心儿科转化医学研究所,上海200127 [4]嘉华药锐科技(北京)有限公司,北京102206 [5]国家癌症中心、国家肿瘤临床医学研究中心、中国医学科学院北京协和医学院肿瘤医院分子肿瘤学国家重点实验室,病因及癌变研究室,北京100021

出　　处：《中华肿瘤杂志》2024年第8期755-763,共9页Chinese Journal of Oncology

基　　金：国家自然科学基金(81771830);北京市自然科学基金(7184238);科技创新2030“—新一代人工智能”重大项目(2020AAA0109504)。

摘　　要：目的探讨临床ⅠA期肺腺癌的基因突变特征及其与患者预后的关系,为早期肺腺癌患者的个体化治疗提供依据。方法收集2007年1月至2012年10月在中国医学科学院肿瘤医院接受手术切除且随访达10年以上或随访期间出现复发或转移的临床ⅠA期肺腺癌患者63例,采用全外显子组测序(WES)技术分析肺癌组织的基因突变谱,采用单因素和多因素Cox回归分析明确患者预后影响因素。结果在随访期间,63例患者中13例(20.6%)出现复发或转移。WES技术分析显示,肺癌组织中表皮生长因子受体突变频率最高,达65.1%(41/63),其次为肿瘤蛋白p53、异常类脂肪酸1、低密度脂蛋白受体相关蛋白1B、雷帕霉素机械靶点、磷脂酰肌醇4,5-双磷酸3-激酶催化亚单位γ(PIK3CG)及与SWI/SNF相关基质相关的依赖于肌动蛋白的染色质调节因子亚家族A成员4,突变频率分别为30.2%(19/63)、20.6%(13/63)、15.9%(10/63)、15.9%(10/63)、15.9%(10/63)和15.9%(10/63)。多因素Cox回归分析显示,PIK3CG突变(HR=21.52,95%CI:3.19~145.01)、平滑蛋白(SMO)突变(HR=35.28,95%CI:3.12~398.39)、β-连环蛋白1(CTNNB1)突变(HR=332.86,95%CI:15.76~7029.05)、集落刺激因子1受体(CSF1R)突变(HR=8109.60,95%CI:114.19~575955.17)、v-Raf小鼠肉瘤病毒癌基因同源B(BRAF)突变(HR=23.65,95%CI:1.86~300.43)为临床ⅠA期肺腺癌患者预后的独立危险因素。结论PIK3CG、SMO、CTNNB1、CSF1R、BRAF基因突变与临床ⅠA期肺腺癌的远期复发和转移密切相关,应给予具有这些基因突变的肺腺癌患者更为密切的临床关注。Objective To explore the gene mutation characteristics and the relationship between gene mutations and long-term prognosis in clinical stageⅠA lung adenocarcinoma patients.Methods A retrospective analysis was conducted on 63 clinical stageⅠA lung adenocarcinoma patients who underwent surgical resection at the Cancer Hospital of the Chinese Academy of Medical Sciences from January 2007 to October 2012,with documented postoperative recurrence or metastasis,as well as those who had a follow-up duration of 10 years or more without recurrence or metastasis.Whole exome sequencing(WES)technology was used to analyze the gene mutation profiles in tumor tissues and univariate and multivariate Cox regression analysis were used to clarify the influencing factors for patient prognosis.Results After long term follow-up,13 out of the 63 patients(21%)experienced recurrence or metastasis.WES technology analysis revealed that the most common tumor related gene mutations occurred in epidermal growth factor receptor(EGFR),with a mutation rate of 65.1%(41/63),followed by tumor protein p53(TP53),fatatypical cadherin 1(FAT1),low density lipoprotein receptor-related protein 1B(LRP1B),mechanistic target of rapamycin(MTOR),phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma(PIK3CG),and SWI/SNF related,matrix associated,actin dependent regulator of chromatin,subfamily A,member 4(SMARCA4),with mutation rates of 30.2%(19/63),20.6%(13/63),15.9%(10/63),15.9%(10/63),15.9%(10/63),and 15.9%(10/63),respectively.Multivariate Cox regression analysis showed that PIK3CG mutations(HR=21.52,95%CI:3.19-145.01),smoothened(SMO)mutations(HR=35.28,95%CI:3.12-398.39),catenin beta 1(CTNNB1)mutations(HR=332.86,95%CI:15.76-7029.05),colony stimulating factor 1 receptor(CSF1R)mutations(HR=8109.60,95%CI:114.19-575955.17),and v-Raf murine sarcoma viral oncogene homolog B(BRAF)mutations(HR=23.65,95%CI:1.86-300.43)were independent risk factors affecting the prognosis of clinical stageⅠA lung adenocarcinoma patients.Conclusions PIK3CG,SMO,CTNNB

关 键 词：肺肿瘤 腺癌 基因突变 预后 

分 类 号：R734.2[医药卫生—肿瘤]