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《中华肺部疾病杂志》[ISSN:1006-6977/CN:61-1281/TN]

卷:

期数:

2021年06期

页码:

711-716

栏目:

论著

出版日期:

2021-12-20

文章信息/Info

Title:

Relationship between EGFR gene 19 th and 21 th exons mutation and clinicopathological features, prognosis of lung adenocarcinoma

作者:

褚代芳; 金发光

710038 西安,空军军医大学唐都医院呼吸与危重症医学科

Author(s):

Chu Daifang;  Jin Faguang.

Department of Respiratory and Critical Care Medicine, Tangdu Hospital, Air Force Military Medical University, Xi'an 710038, China

关键词:

肺腺癌;  表皮生长因子受体;  外显子突变;  病理特征

Keywords:

Lung adenocarcinoma;  Epidermal growth factor receptor;  Exon mutation;  Pathological feature

分类号:

R734.2

DOI:

10.3877/cma.j.issn.1674-6902.2021.06.002

摘要:

目的 分析肺腺癌表皮生长因子受体(EGFR)基因19、21外显子突变与临床病理特征及预后的关系。方法 回顾性分析2017年1月至2018年6月100例经病理证实为肺腺癌的患者临床资料与标本,采用PCR-ARMS 技术检测标本EGFR 基因19、21外显子突变情况,分析EGFR 基因突变与临床病理特征及预后的关系。结果 100例肺腺癌标本共检测出47例EGFR突变,突变率为47.00%,其中第19号外显子突变20例(42.55%),包括6种形式的突变,以核苷酸框架缺失为主,最常见的类型为核苷酸从2234-2248位缺失15bp的delE746-A750突变,共11例,占55.00%; 第21号外显子突变27例(57.45%),包括5种形式的突变,均是碱基置换突变,最常见的类型为2573位点的T被G取代的L858R,共17例,占62.96%; 女性、无吸烟史、临床分期Ⅰ期患者EGFR19与EGFR21突变率高于其他患者(P<0.05); Logisitic回归分析显示性别、吸烟史、肿瘤直径、临床病理分期是影响EGFR19、EGFR21突变的因素。100例肺腺癌患者全部获得有效随访,EGFR19突变患者2年无进展生存率、总生存率分别为80.00%、85.00%,未突变患者分别为65.00%、73.75%; EGFR21突变患者2年无进展生存率、总生存率分别为81.48%、92.59%,未突变患者分别为63.01%、69.86%; 女性、临床分期较早、无淋巴结转移、发生EGFR21突变患者2年生存率低于其他患者(P<0.05); Logisitic回归分析显示男性、临床分期较晚、有淋巴结转移、EGFR21未突变是肺腺癌患者不良预后的独立危险因素。结论 肺腺癌EGFR基因19、21外显子突变与性别、吸烟史、肿瘤直径、临床分期有关,同时也是预测预后的有效方法。

Abstract:

Objective To explore the relationship between epidermal growth factor receptor(EGFR)gene19 th and 21 th exons mutation and clinicopathological features, prognosis of lung adenocarcinoma. Methods The clinical data and specimens of 100 patients who were pathologically confirmed with lung adenocarcinoma from January 2017 to June 2018 were retrospectively analyzed. PCR-ARMS technique was applied to detect the mutation of EGFR gene 19 th and 21 th exons. The relationship between EGFR gene mutation and clinicopathological features, prognosis was analyzed. Results Among the 100 lung adenocarcinoma specimens, there were 47 cases with EGFR mutation, with mutation rate of 47.00%, Among them, there were 20 cases(42.55%)with 19 th exon mutation, including 6 types of mutations, which were mainly on nucleotide framework deletions. And the most common type was delE746-A750 mutation with 15 bp deletion within nucleotide 2234-2248(11 cases, 55.00%). And there were 27 cases(57.45%)with 21 th exon mutation, including 5 types of mutations, all of which were base substitution mutations. The most common type was L858R where T was replaced by G at 2573 locus(17 cases, 62.96%). The mutation rates of EGFR19 and EGFR21 in patients with female gender, without smoking history, and with clinical staging at stage I were higher than those in the other patients(P<0.05). Logisitic regression analysis showed that gender, smoking history, tumor diameter and clinical pathological stage were related with mutation of EGFR19 and EGFR21. All the 100 patients with lung adenocarcinoma were followed up effectively. The 2-year progression-free survival(PFS)rate and overall survival(OS)rate in EGFR19 mutation patients and non-mutation patients were(80.00%, 85.00%)and(65.00%, 73.75%), respectively. The 2-year PFS rate and OS rate in EGFR21 mutation patients and non-mutation patients were(81.48%, 92.59%)and(63.01%, 69.86%), respectively. The 2-year survival rate in patients with female gender, early clinical staging, without lymph node metastasis, and with EGFR21 mutation was lower than that in the other patients(P<0.05). Logisitic regression analysis showed that male gender, late clinical staging, lymph node metastasis and EGFR21 non-mutation were independent risk factors of poor prognosis of lung adenocarcinoma patients. Conclusion The mutations of EGFR gene 19 th and 21 th exons in lung adenocarcinoma are related to gender, smoking history, tumor diameter and clinical stage, which are are also effective methods for predicting prognosis.

参考文献/References:

1 钱桂生. 肺癌不同病理类型发病率的变化情况及其原因[J/CD]. 中华肺部疾病杂志(电子版), 2011, 4(1): 1-5.
2 康小红, 高园园, 王 颖, 等. 肺腺癌转移相关转录本1诱导肺癌HCC827细胞对奥希替尼耐药的作用机制[J]. 中华肿瘤杂志, 2019, 41(4): 257-262.
3 Siegel RL, Miller KD, Jemal A, et al. Cancer statistics 2018[J]. CACancer J Clin, 2018, 68(1): 7-30.
4 Sang-ji Choi, SeongKweon Hong, Gibong Chae, et al. Solitary colonic metastasis from primary lung adenocarcinoma first presenting as intestinal obstruction: A case report[J]. Med, 2019, 98(3): 140-142.
5 Zeng QP, Zhao J. Advances in clinical research on sub-types of lung adenocarcinoma based on the new interna-tional classification[J]. J Oncol, 2019, 25(5): 387-393.
6 周方元, 李 艳. 肺腺癌患者表皮生长因子受体基因突变以及不同性别、年龄、转移患者突变分析[J]. 微循环学杂志, 2019, 29(4): 43-46.
7 陈羽中, 沈 波. EGFR敏感突变晚期非小细胞肺癌的靶向治疗进展[J]. 临床肿瘤学杂志, 2019, 24(5): 454-462.
8 Sakuma Y. Epithelial-to-mesenchymal transition and its role in EGFR-mutant lung adenocarcinoma and idiopathic pulmonary fibrosis[J]. Pathol Int, 2017, 67(8): 379-388.
9 Sheng-Kai Liang, Meng-Rui Lee, Wei-Yu Liao, et al. Prognostic factors of afatinib as a first-line therapy for advanced EGFR mutation-positive lung adenocarcinoma: A real-world, large cohort study[J]. Oncotarget, 2018, 9(34): 23749-23760.
10 卢鉴财, 黄 俊, 徐韫健, 等. Super-ARMS法在检测非小细胞肺癌EGFR基因突变中的应用分析[J]. 热带医学杂志, 2019, 22(4): 430-433.
11 Truini A, Starrett JH, Stewart T, et al. The EGFR exon 19 mutant L747-A750>P exhibits distinct sensitivity to tyrosine kinase inhibitors in lung adenocarcinoma[J]. Clin Cancer Res, 2019, 25(21): 6382-6391.
12 Murano C, Igarashi A, Yamauchi K, et al. Osimertinib as treatment for EGFR exon 20 insertion-positive lung adeno-carcinoma[J]. Excli J, 2019, 18(10): 893-898.
13 Travis WD, Brambilla E, Nicholson AG, et al. The 2015 worldhealth organization classification of lung tumors: impact ofgenetic, clinicalandradiologicadvancessince the 2004 clas-sification[J]. J Thorac Oncol, 2015, 10(9): 1243-1260.
14 Yunqiang Nie, Wei Gao, Na Li, et al. Relationship between EGFR gene mutation and local metastasis of resectable lung adenocarcinoma[J]. World J Surg Oncol, 2017, 15(1): 55.
15 Gao N, Xi Y, Wang Y, et al. Epidermal growth factor recepter, KRASand BRAF gene mutations and their correlation with clinicopathological characteristics in non-small-cell lung cancer[J]. Cancer Research Clinic, 2015, 27(8): 551-554.
16 Shi Y, Li J, Zhang S, et al. Molecular Epidemiology of EGFR mutationsinasian patients with advanced non-small-cell lung cancer of adenocarcinoma histology-Mainland China subset analysis of the PIO-NEER study[J]. PLoS One, 2015, 10(11): e0143515.
17 赵 静, 高 洁, 郭李平, 等. 754 例Ⅰ期-Ⅲa 期可手术切除非小细胞肺癌患者EGFR和KRAS基因突变状态及其临床意义[J]. 中国肺癌杂志, 2017, 20(9): 617-622.
18 黄海涛, 李 灵. 去甲基化酶ALKBH5在肺腺癌组织中的表达及其与细胞增殖的关系[J]. 肿瘤, 2018, 38(6): 572-580.
19 陆如建, 褚红军, 尤庆生, 等. EGFR 基因突变及 ERCC1、RRM1 表达在非小细胞肺癌精准化治疗中的应用价值[J]. 交通医学, 2017, 31(2): 115-120.
20 唐珊珊, 李 莉, 袁双虎. EGFR 19/21位点突变与597例非小细胞肺癌患者中发生脑转移的关联分析[J]. 中华肿瘤防治杂志, 2019, 46(10): 26-27.
21 孔 君, 杨 雪, 孔 辉, 等. 2 394例肺腺癌患者EGFR及ALK驱动基因分析[J]. 南京医科大学学报(自然科学版), 2020, 40(5): 675-680, 719.
22 Alikhanyan K, Chen Y, Kraut S, et al. Targeting alveolarmacrophages shows better treatment response than deletion ofinterstitial macrophages in EGFR mutant lung adenocarcinoma[J]. Immun Inflamm Dis, 2020, 8(2): 181-187.
23 凌止鸿, 李月明, 陈 晶, 等. 非小细胞肺癌患者表皮生长因子受体突变对靶向治疗的疗效影响及生存分析[J]. 实用癌症杂志, 2017, 32(2): 207-209.
24 Tsiambas E, Lefas AY, Georgiannos SN, et al. EGFR genederegulation mechanisms in lung adenocarcinoma: a molecular review[J]. Pathol Res Pract, 2016, 212(8): 672-676.
25 汪 强, 范晓云, 徐 轲, 等. 免疫组化检测肺腺癌病人表皮生长因子受体-19、21和甲状腺转录因子-1与临床特征关系[J]. 安徽医药, 2017, 21(7): 1276-1278.
26 叶胜兵, 李 锐, 时姗姗. 肺腺癌患者表皮生长因子受体(EGFR)酪氨酸激酶抑制剂获得性耐药前后EGFR基因状态变化情况探讨[J]. 中华病理学杂志, 2017, 46(2): 98-101.
27 Gubensek, Jakob, Buturovic-Ponikvar, et al. Heparin-free regional anticoagulation: there are significant differences between citrate-containing dialysate and regional citrate anticoagulation[J]. Crit Care Med, 2018, 46(8): 17-18.
28 葛 佳, 李 磊, 姚小红, 等. 重庆地区924例非小细胞肺癌EGFR基因突变分析[J]. 临床与实验病理学杂志, 2019, 25(7): 772-775.
29 朱晓丹, 陈成水. 青年肺腺癌EGFR、KRAS基因突变与临床特点及预后的关系研究[J]. 新医学, 2017, 48(7): 96-97.
30 张海艳, 胡春生, 刘 斌, 等. 中国非小细胞肺癌BRAF V600、EGFR 基因突变患者的临床病理特征分析[J]. 临床肿瘤学杂志, 2019, 14(6): 51-52.
31 Hu M, Zhang B, Xu J, et al. Clinical outcomes of differentgenerations of egfr tyrosine kinase inhibitors in advancedlung adenosquamous carcinoma[J]. Mol Diagn Ther, 2019, 23(6): 773-779.

备注/Memo

备注/Memo:

基金项目: 国家自然科学基金资助项目(81570067)
通信作者: 金发光, Email: jinfag@fmmu.edu.cn

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更新日期/Last Update: 2021-12-20