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老年肺腺癌患者分子遗传学特点分析

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目的 利用下一代测序技术(NGS)分析老年肺腺癌患者的分子遗传学特点及相关性,为靶向治疗提供临床依据。方法 选取 2021 年 1 月至 2023 年 12 月于山东第一医科大学附属省立医院就诊的 333 例老年肺腺癌患者为研究对象,患者年龄≥65 岁,所有患者均经病理组织学确诊,数据取自初诊治疗前的组织标本检测结果。采用NGS平台进行多基因突变检测,对《中华医学会肺癌临床诊疗指南(2023 版)》推荐检测的 9 种驱动基因,即表皮生长因子受体(EGFR)、间变性淋巴瘤激酶(ALK)、ROS原癌基因酪氨酸蛋白激酶 1(ROS1)、鼠类肉瘤病毒癌基因(KRAS)、B-Raf丝氨酸/苏氨酸蛋白激酶(BRAF)、Erb-B2 受体酪氨酸激酶 2(ERBB2)、Ret原癌基因(RET)、Met原癌基因(MET)、神经营养因子受体络氨酸激酶(NTRK)以及部分少见突变基因,进行临床病理学、驱动基因突变状态等归纳分析。结果 9 种驱动基因总阳性率为 41。14%(137 例),其中EGFR为主要驱动基因,突变频率为 36。04%(120 例),其他基因突变频率为KRAS 15。92%(53 例),ERBB2 2。10%(7 例),EML4-ALK 1。80%(6 例),BRAF 1。50%(5 例),MET 1。20%(4 例),RET 0。30%(1 例)。13 种少见突变基因与驱动基因共突变种类集中于EGFR、KRAS、抑癌基因TP53(TP53)三种共突变形式,其中磷脂酰肌醇激酶催化α多肽基因(PIK3CA)、U2 小核RNA辅助因子 1(U2AF1)以及乳腺癌 1 号基因(BRCA1)仅以共突变形式出现,人第 10 号染色体缺失的磷酸酶(PTEN)的共突变形式仅为与EGRF共突变,BRCA1、丝氨酸/苏氨酸激酶 11(STK11)、富AT互作域 1A基因(ARID1A)以及N-Ras原癌基因(NRAS)的共突变形式仅为与KARS共突变。通过对癌症基因组图谱计划(TCGA)数据库中肺腺癌数据进行生物信息学统计分析,13 种少见突变基因在肿瘤相关信号通路中正常化富集评分(NES)得分均较高,证明其均参与肿瘤的发生、发展过程。结论 应用NGS检测的9种驱动基因分子遗传学数据可以有效地显示肺腺癌的驱动基因分布及特点,尤其是了解少见突变基因以及共突变基因遗传学特点将更有利于指导临床治疗。
Molecular genetic characteristics of elderly patients with lung adenocarcinoma
Objective Using the NGS sequencing data to analyze the molecular genetic characteristics and correlation of elderly lung adenocarcinoma patients,to provide clinical evidence for targeted therapy.Methods 333 elderly(≥65-years-old)lung adenocarcinoma patients who were treated at Shandong Provincial Hospital Affiliated to Shandong First Medical University from January 2021 to December 2023 were selected as the study subjects.All patients were confirmed by surgical pathology,and the data were obtained from tissue specimen tissue testing results before initial treatment.Using the NGS platform for multi-gene mutation detection,including the nine driving genes recommended for detection in the"Chinese Medical Association Guideline Clinical Diagnosis and Treatment of Lung Cancer(2023 edition)".Specifically EGFR,ALK,ROS1,KRAS,BRAF,ERBB2,RET,MET and NTRK,which analyzed the retrospective analysis of patient demographics,clinical pathology,and driving gene mutation status.Results The total positive rate of 9 driving genes was 41.14% (137 cases),among which EGFR was the main driving gene with a mutation frequency of 36.04% (120 cases),other mutation frequency genes:KRAS 15.92% (53 cases),ERBB2(HER2)2.10% (7 cases),EML4-ALK 1.80% (6 cases),BRAF 1.50% (5 cases),MET 1.20% (4 cases),and RET 0.30% (1 case).The results showed that 13 rare types of co-mutations with driver genes were concentrated in three co-mutation forms such as EGFR,KRAS,and TP53.PIK3CA,U2AF1,and BRCA1 only appeared in co-mutation form,PTEN only showed EGRF co-mutation form,and BRCA1,STK11,ARID1A,and NRAS only showed KARS co-mutation form.Through bioinformatics statistical analysis of lung adenocarcinoma data in the TCGA database,it was found that 13 rare mutated genes had high NES scores in tumor related signaling pathways,indicating their involvement in the occurrence and development of tumors.Conclusions By analyzing the molecular genetic characteristics and mutation gene correlation of elderly lung adenocarcinoma patients,the molecular genetic data of 9 recommended driving genes could reflect the distribution and correlation of driving genes in lung adenocarcinoma.Especially,further understanding of the distribution of rare genes will be more conducive to guiding clinical treatment.

Next generation sequencingElderly patientsLung adenocarcinomaTargeted therapy

刘珏、许瑞、孙有伟

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山东第一医科大学附属省立医院临床医学检验部,山东 济南 250021

山东第二医科大学基础医学院,山东 潍坊 261042

山东第一医科大学附属省立医院介入诊疗科,山东 济南 250021

二代测序 老年 肺腺癌 靶向治疗

2024

新医学
中山大学

新医学

CSTPCD
影响因子:0.8
ISSN:0253-9802
年,卷(期):2024.55(11)