肺泡灌洗液外泌体表皮生长因子受体基因突变检测对晚期非小细胞肺癌患者的临床意义
收稿日期: 2023-06-21
网络出版日期: 2024-01-24
基金资助
遵义市科技计划项目【编号:遵市科合HZ字(2021)181号(Gzwkj2021-526);黔科合基础-ZK[2022]300
Clinical significance of detection of EGFR mutation in alveolar lavage fluid exosome of patients with advanced non⁃small cell lung cancer
Received date: 2023-06-21
Online published: 2024-01-24
目的 通过对比分析晚期非小细胞肺癌(NSCLC)患者支气管肺泡灌洗液(BALF)外泌体、血液和肺癌组织3种标本表皮生长因子受体(EGFR)基因突变情况,评估支气管肺泡灌洗液外泌体标本是否适合应用于临床靶向治疗前的患者筛检,为晚期NSCLC患者尽早个体化治疗提供新的思路和筛检方法。 方法 回顾性分析2021年5月至2023年5月贵州航天医院呼吸与危重症医学科78例晚期NSCLC患者利用扩增阻滞突变系统法(ARMS)检测支气管泡灌洗液外泌体、血液、肺癌组织标本EGFR基因突变的结果并以肺癌组织标本结果为标准进行相互比较。 结果 支气管肺泡灌洗液外泌体、血液、肺癌组织标本分别检出EGFR突变型33、25、38例,EGFR基因野生型分别42、53、40例,检测突变率分别为42.3%(33/78)、32.1%(25/78)、48.7%(38/78)。支气管肺泡灌洗液检测无结果3例,假阴性率6.4%(5/78),血液检测假阴性率16.7%(13/78)。支气管肺泡灌洗液外泌体标本EGFR基因突变的检测符合率86.8%(33/38),血液标本检测符合率65.8%(25/38)。 结论 支气管肺泡灌洗液外泌体标本检测EGFR基因突变与血液、肺癌组织标本检测具有一致性(P > 0.05),优于血液标本,适用于临床靶向治疗前的患者筛选,为晚期NSCLC患者尽早个体化治疗决策提供了新的思路和筛检方法。
杨昌恒 , 陈颖 , 张中元 , 马庆庆 . 肺泡灌洗液外泌体表皮生长因子受体基因突变检测对晚期非小细胞肺癌患者的临床意义[J]. 实用医学杂志, 2024 , 40(1) : 48 -52 . DOI: 10.3969/j.issn.1006-5725.2024.01.009
Objective To compare and analyze the gene mutation of EGFR of bronchoalveolar lavage fluid (BALF) exosome, serum and lung cancer tissue specimens of patients with advanced non?small cell lung cancer (NSCLC) and assess whether the BALF exosome specimens are suitable for screening before clinical targeted therapy, to provide new ideas and screening methods for early individualized treatment of advanced NSCLC patients. Methods BALF exosomes, serum and lung cancer tissue specimens EGFR gene mutations of 78 cases with advanced NSCLC were detected by using amplification refractory mutation system(ARMS) method in Department of Respiratory and Critical Care Medicine in our hospital from May 2021 to May 2023, and the results were retrospectively analyzed. A comparative analysis of the specimens was conducted using lung cancer tissue specimens as benchmarks. Results A total of 33, 25 and 38 cases of EGFR gene mutation and 42, 53 and 40 cases of EGFR wild type were detected in BALF exosomes, serum and lung cancer tissues specimens respectively. The mutation rate of EGFR gene was 42.3%(33/78, 32.1 %(25/78)and 48.7%(38/78)in BALF exosomes, serum and lung cancer tissues specimens respectively. EGFR detection showed no results in 3 cases and the false?negative rate was 6.4% (5/78) in BALF specimen, and false?negative rate was 16.7% (13/78) in serum. The detection coincidence rate of EGFR mutation was 86.8% (33/38) in BALF exosomes specimen, and 65.8% (25/38) in serum. Conclusions EGFR gene mutation rate in BALF exosome specimen is consistent with that in serum and lung cancer tissue samples, showing no statistical significance (P > 0.05). It is superior to serum specimen and suitable for patient screening before targeted therapy and provides new ideas and screening methods for early individualized treatment decisions of advanced NSCLC patients.
Key words: exosome; EGFR; ARMS; advanced NSCLC; BALF
| 1 | MILLER K D, NOGUEIRA L, MARIOTTO A B, et al.Cancer treatment and survivorship statistics,2019[J]. CA Cancer J Clin,2019,69(5):363-385. |
| 2 | GUO Q N, LIU L W, CHEN Z L, et al. Current treatments for non-small cell lung cancer [J]. Front Oncol,2022,12:945102-945102. |
| 3 | 李改平,郭青云,朱贵荣,等. 不同铂类物质对晚期非小细胞肺癌患者的临床疗效观察[J]. 实用癌症杂志,2016,31(11):1875-1878. |
| 4 | BOOLELL V, ALAMGEER M, WATKINS D N,et al. The evolution of therapies in non-small cell lung cancer [ J] . Cancers ( Basel),2015,7(3) :1815-1846 . |
| 5 | 洪雅萍,黄韵坚,黄漳州,等. EGFR突变的晚期非小细胞肺癌患者接受一代TKI靶向治疗的效果及预后预测因子分析[J]. 中国癌症杂志,2022,32(7):624-634. |
| 6 | 杜敏娟,徐晓光.奥西替尼靶向治疗对晚期非小细胞肺癌患者的疗效[J].中国老年学杂志,2021,41(11):2286-2289. |
| 7 | BRAINARD J, FARVER C. The diagnosis of non-small cell lung cancer in the molecular era [J]. Mod Pathol, 2019,32(): 16-26 . |
| 8 | RAMALINGAM S, BELANI C. Systemic chemotherapy for advanced non-small cell lung cancer : recent advances and future directions [J]. Oncologist, 2008,13( ): 5- 13. |
| 9 | PARVATHANENI V, KULKRRMI S N, SHUKLA K S, et al. Systematic Development and Optimization of Inhalable Pirfenidone Liposomes for Non-Small Cell Lung Cancer Treatment[J]. Pharmaceutics, 2020,12(3):206. |
| 10 | ZHU C N C, ZHANG W H, CHEN L M, et al.Frontiers of ctDNA, targeted therapies, and immunotherapy in non-small-cell lung cancer[J]. Transl Lung Cancer Res, 2020,9(1):111-138 |
| 11 | WEI C, CHEN H D, WEN Y Y, et al. Changing profiles of cancer burden worldwide and in China: a secondary analysis of the global cancer statistics 2020[J]. Chin Med J(Engl), 2021,134(7):783-791. |
| 12 | 贺荣芝,刘川,蔡婧,等. 非小细胞肺癌组织、血液及胸水EGFR基因突变分析[J]. 临床与实验病理学杂志, 2019, 35(4): 421-424. |
| 13 | 成瑶. NSCLC患者EGFR、ALK基因突变状态、病理特征及与病情转归的关系分析[J]. 临床研究,2021,29(5):16-18. |
| 14 | ILARIA A, NIKI K, PIERFRANCO C, et al. Therapeutic approaches for T790M mutation positive non-small-cell lung cancer[J]. Expert Rev Anticancer Ther, 2018,18(10):1021-1030. |
| 15 | ZHAO Y X, WANG H Y, HE C W, et al. Drug resistance of targeted therapy for advanced non-small cell lung cancer harbored EGFR mutation: from mechanism analysis to clinical strategy[J]. J Cancer Res Clin, 2021,147(12):3653-3669. |
| 16 | LI N, XU Y J, FAN Y . et al. Current Advance in Targeted Treatment and Immunotherapy for BRAF-mutant Advanced Non-small Cell Lung Cancer [J]. Chin J Cancer, 2021,24(10):714-722. |
| 17 | ABHISHEK D, SWSTTIKA P. Exosome-based cancer stem cell communication: Implication for detecting and eliminating cancer stem cells[J]. MedComm Futur Med, 2022,1(2)e23. |
| 18 | HASSANPOUR M, REZABAKHSH A, REZAIE J,et al. Exosomal cargos modulate autophagy in recipient cells via different signaling pathways [J]. Cell Biosci, 2020,10(1):92. |
| 19 | 颜晓慧,安泰学,覃思华,等. 血清外泌体miR-21在肺癌中的表达水平及其诊断效能[J]. 实用医学杂志, 2017,33(16):2666-2669. |
| 20 | 冉凤英,彭伟东,陈浩,等. 血浆外泌体miRNA-221对非小细胞肺癌的诊断价值[J]. 实用医学杂志, 2021,37(1):91-95. |
| 21 | SONG M J, ZHANG X W, GAO Y Z, et al. RNA sequencing reveals the emerging role of bronchoalveolar lavage fluid exosome lncRNAs in acute lung injury[J]. PeerJ, 2022,(10):13159. |
| 22 | HE N, YAN H Y, DENG X Y, et al. MiR-223-3p-loaded exosomes from bronchoalveolar lavage fluid promote alveolar macrophage autophagy and reduce acute lung injury by inhibiting the expression of STK39[J]. Hum cell, 2022,35(6):1736-1751. |
| 23 | HAN S Y, GUO Y R, LUO X W, et al. Clinical value of alveolar lavage supernatant specimens in the detection of the EGFR gene mutation in patients with non-small cell lung carcinoma[J]. Transl Cancer Res, 2022,11(5):1188-1194. |
| 24 | 周小昀,李龙芸,崔巍,等. 检测肺癌患者血清游离DNA的EGFR基因点突变与EGFR-TKI疗效的相关性分析[J]. 癌症进展, 2011, 9(1):13-18. |
| 25 | 李迎雪,温文娟,韩琳,等. 应用ARMS检测不同类型的肺腺癌标本EGFR基因突变[J]. 临床与实验病理学杂志, 2015,31(6):700-702. |
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