原发性肺癌患者结核分枝杆菌感染调查及Notch信号通路表达分析

勾蓉, 陈琪, 张海燕, 梁玲, 罗含荑, 梁静秋

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重庆医科大学学报 ›› 2024, Vol. 49 ›› Issue (02) : 193-197. DOI: 10.13406/j.cnki.cyxb.003431
临床研究 DOI:10.13406/j.cnki.cyxb.003431

原发性肺癌患者结核分枝杆菌感染调查及Notch信号通路表达分析

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An investigation of Mycobacterium tuberculosis infection and expression of the Notch signaling pathway in patients with primary lung cancer

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摘要

目的 探究原发性肺癌患者结核分枝杆菌(Mycobacterium tuberculosis,MTB)感染调查及Notch信号通路表达情况。 方法 选取2022年1月至2022年6月在重庆大学附属肿瘤医院接受根治术治疗的96例原发性肺癌患者为研究对象,采用原位分子杂交技术和抗酸染色法对肺组织的MTB及其L型进行检测,药敏试验分析其耐药性,测序鉴定靶基因位点突变情况,蛋白印迹法检测肺组织Notch1、Notch2和Notch3蛋白表达。 结果 96例原发性肺癌组织标本MTB-L型阳性率为38.54%(37/96),阳性患者痰标本共分离出MTB-L菌株68株;分离MTB-L型菌株对一线抗结核药物耐药率为60.29%(41/68),其中对异烟肼、链霉素、利福平及乙胺丁醇联合使用耐药率最高(22.06%);分离MTB-L型菌株对二线抗结核药物耐药率为36.76%(25/68),其中对氧氟沙星单一用药耐药率最高(14.70%);MTB-L型菌株药物靶基因突变率前3位分别为异烟肼靶基因katG S315T(45.58%)、链霉素靶基因rpsL K43R(42.65%)、利福平靶基因rpoB S450L(20.59%);MTB-L型感染阳性患者肺组织中Notch1、Notch2、Notch3蛋白相对表达量高于MTB-L型阴性者(P<0.05)。 结论 原发性肺癌患者MTB感染类型主要为L型,其耐药形势严峻,合并MTB-L型感染患者存在Notch信号通路的异常激活。

Abstract

Objective To explore Mycobacterium tuberculosis(MTB) infection and the expression of the Notch signaling pathway in patients with primary lung cancer. Methods A total of 96 patients with primary lung cancer who underwent radical surgery at Chongqing University Cancer Hospital between January 2022 and June 2022 were enrolled as research subjects. MTB and its L-forms in the lung tissue were detected using in situ molecular hybridization and acid-fast staining. Drug resistance was analyzed using a drug susceptibility test. Mutations at the sites of target genes were identified using sequencing. The expressions of Notch1,Notch2 and Notch3 proteins in the lung tissue were determined using Western blot. Results Of the 96 patients with primary lung cancer,the positive rate of MTB-L forms was 38.54%(37/96),with 68 MTB-L strains isolated from the sputum samples of the positive patients. The resistance rate of the isolated MTB-L strains to first-line anti-tuberculosis drugs was 60.29%(41/68),with the highest drug resistance rate of 22.06% for the combination of isoniazid,streptomycin,rifampicin,and ethambutol. The resistance rate of the isolated MTB-L strains to second-line anti-tuberculosis drugs was 36.76%(25/68),with the highest drug resistance rate of 14.70% for ofloxacin alone. The target genes with the top three mutation rates at the drug sites of the MTB-L strains were isoniazid katG S315T(45.58%),streptomycin rpsL K43R(42.65%),and rifampicin rpoB S450L(20.59%). The relative expression levels of Notch1,Notch2,and Notch3 proteins in the lung tissue of patients with positive MTB-L infections were higher than those in the lung tissue of patients with negative MTB-L infections(P<0.05). Conclusion MTB infection in patients with primary lung cancer is mainly caused by MTB L-forms,and drug resistance is severe. Abnormal activation of the Notch signaling pathway is observed in patients with MTB-L infection.

关键词

原发性肺癌 / 结核分枝杆菌 / 耐药性 / 基因突变 / Notch信号通路

Key words

primary lung cancer / mycobacterium tuberculosis / drug resistance / gene mutation / Notch signaling pathway

中图分类号

R181

引用本文

导出引用
勾蓉 , 陈琪 , 张海燕 , . 原发性肺癌患者结核分枝杆菌感染调查及Notch信号通路表达分析. 重庆医科大学学报. 2024, 49(02): 193-197 https://doi.org/10.13406/j.cnki.cyxb.003431
Gou Rong, Chen Qi, Zhang Haiyan, et al. An investigation of Mycobacterium tuberculosis infection and expression of the Notch signaling pathway in patients with primary lung cancer[J]. Journal of Chongqing Medical University. 2024, 49(02): 193-197 https://doi.org/10.13406/j.cnki.cyxb.003431

参考文献

1
Oliver AL .Lung cancer:epidemiology and screening[J]. Surg Clin North Am2022102(3):335-344.
2
Laurent PA Martin E Thariat J,et al. Radiotherapy for primary tumor in lung cancer with synchronous metastases:overview from the past and proposal for the future[J]. Cancer Radiother202024(6/7):554-558.
3
Preda M Tănase BC Zob DL,et al. The bidirectional relationship between pulmonary tuberculosis and lung cancer[J]. Int J Environ Res Public Health202320(2):1282.
4
许毓贞,杨清銮,刘袁媛,等. 综合性医院结核分枝杆菌血培养阳性患者的临床特征分析[J]. 中华传染病杂志201937(3):144-148.
Xu YZ Yang QL Liu YY,et al. Clinical characteristics of patients with positive blood culture for Mycobacterium tuberculosis in a general hospital[J]. Chin J Infect Dis201937(3):144-148.
5
赵仕佳,李 峰,肖成林,等. nm23蛋白在前列腺癌患者中的表达与结核菌L型感染的相关性研究[J]. 中华医院感染学杂志201929(9):1392-1395.
Zhao SJ Li F Xiao CL,et al. Expression of nm23 protein in prostate cancer patients and its correlation Mycobacterium tuberculosis L-form infection[J]. Chin J Nosocomiology201929(9):1392-1395.
6
Guo MZ Niu Y Xie M,et al. Notch signaling,hypoxia,and cancer[J]. Front Oncol202313:1078768.
7
Shi QH Wang JY Yang Z,et al. CircAGFG1modulates autophagy and apoptosis of macrophages infected by Mycobacterium tuberculosis via the Notch signaling pathway[J]. Ann Transl Med20208(10):645.
8
Zhang H Yang YK Li XC,et al. Targeting the Notch signaling pathway and the Notch ligand,DLL3,in small cell lung cancer[J]. Biomedecine Pharmacother2023159:114248.
9
王 丽. 中国原发性肺癌诊疗规范(2015年版)解读[J]. 世界临床药物201637(7):433-436.
Wang L. Interpretation of Chinese lung cancer treatment guidelines(2015 edition)[J]. World Clin Drugs201637(7):433-436.
10
中华结核和呼吸杂志编辑委员会. 结核分枝杆菌L型的检测方法(试行)[J]. 中华结核和呼吸杂志200326(2):67-69.
Editorial Board of Chinese Journal of Tuberculosis and Respiratory Diseases. Detection method for L-type Mycobacterium tuberculosis (trial) [J]. Chin J Tuberc Respir Dis200326(2):67-69.
11
王 伟,刘京铭,李传友. WHO 2014年版《耐药结核病规划管理指南伙伴手册》解读之五(耐药结核病实验室检测)[J]. 中国防痨杂志201537(6):655-658.
Wang W Liu JM Li CY. Interpretation of the 2014 edition of the WHO 2014 edition of "Drug-resistant tuberculosis program management guidelines partner manual" interpretation five (laboratory detection of drug-resistant tuberculosis) [J]. Chin J Antituberc201537(6):655-658.
12
Crowther RR Qualls JE. Metabolic regulation of immune responses to Mycobacterium tuberculosis:a spotlight on L-arginine and L-tryptophan metabolism[J]. Front Immunol202111:628432.
13
王 娜,朱广艺,艾克拜尔·热合曼,等. 基于PCR检测和基因测序分析的鹿源副结核分枝杆菌鉴定及亚型分型[J]. 中国人兽共患病学报201935(1):85-90.
Wang N Zhu GY Aikebaier R,et al. Identification and subtyping of deer-derived Mycobacterium paratuberculosis based on PCR detection and gene sequencing analysis[J]. Chin J Zoonoses201935(1):85-90.
14
Abudureheman M Simayi R Aimuroula H,et al. Association of Mycobacterium tuberculosis L-formmpb64 gene and lung cancer[J]. Eur Rev Med Pharmacol Sci201923(1):113-120.
15
宁洪叶,蒋贤高,施伎蝉,等. 结核分枝杆菌感染对非小细胞肺癌患者调节性免疫细胞的负向调节作用[J]. 中华危重症医学杂志(电子版),201912(4):240-244.
Ning HY Jiang XG Shi JC,et al. Negative regulation of Mycobacterium tuberculosis infection on regulatory immune cells in patients with non-small cell lung cancer[J]. Chin J Crit Care Med(Electron Ed)201912(4):240-244.
16
阮红刚,付潮泓,许腊梅. 原发性肺癌患者结核分枝杆菌的耐药性检测[J]. 中国感染与化疗杂志201818(5):472-476.
Ruan HG Fu CH Xu LM. Detection of drug resistance of Mycobacterium tuberculosis in patients with primary lung cancer[J]. Chin J Infect Chemother201818(5):472-476.
17
Martelli G Pessatti TB Steiner EM,et al. N-Thio-β-lactams targeting L,D-transpeptidase-2,with activity against drug-resistant strains of Mycobacterium tuberculosis [J]. Cell Chem Biol202128(9):1321-1332.
18
Cervantes J Yokobori N Hong BY. Genetic identification and drug-resistance characterization of Mycobacterium tuberculosis using a portable sequencing device. A pilot study[J]. Antibiotics20209(9):548.
19
高 敏,杨婷婷,李桂莲,等. 基于全基因组测序的我国耐多药结核分枝杆菌耐药突变特征分析[J]. 中华流行病学杂志202041(5):770-775.
Gao M Yang TT Li GL,et al. Analysis of drug resistance mutation characteristics of multidrug-resistant Mycobacterium tuberculosis in my country based on whole-genome sequencing [J]. Chin J Epidemiol202041(5):770-775.
20
张冠磊,马苗苗,兰文静,等. LncRNA-p21调控Notch信号通路对非小细胞肺癌A549细胞增殖、迁移及侵袭的影响[J]. 肿瘤防治研究202148(2):121-126.
Zhang GL Ma MM Lan WJ,et al. Effect of LncRNA-p21 regulating Notch signaling pathway on proliferation,migration and invasion of non-small cell lung cancer A549 cells[J]. Cancer Res Prev Treat202148(2):121-126.
21
冯茂耕,杨双林,罗道文,等. 骨质疏松症大鼠脂肪干细胞成骨能力及Mettl14和Notch1表达的探究[J]. 四川大学学报(医学版)202152(3):423-429.
Feng MG Yang SL Luo DW,et al. Osteogenic capacity and Mettl14 and Notch1 expression of adipose-derived stem cells from osteoporotic rats[J]. J Sichuan Univ Med Sci202152(3):423-429.
22
Huang RX Bai CJ Liu XD,et al. The p53/RMRP/miR122 signaling loop promotes epithelial-mesenchymal transition during the development of silica-induced lung fibrosis by activating the Notch pathway[J]. Chemosphere2021263:128133.
23
Zheng H Zhu XY Gong EH,et al. Luteolin suppresses lung cancer progression through targeting the circ_0000190/miR-130a-3p/notch-1 signaling pathway[J]. J Chemother202335(4):330-342.
24
Ng J Sutherland KD. NOTCH your usual suspect:MYC charged with controlling neuroendocrine cell-fate in small cell lung cancer[J]. Cancer Cell202038(1):17-20.
25
李 良. 结核菌脂阿拉伯甘露糖通过Notch1介导结核免疫逃避的实验研究[J]. 中国现代医生201856(11):22-25,29.
Li L. Experimental study on tuberculosis immune escape medicated by tuberculosis lipid Arabia mannose via Notch 1[J]. China Mod Dr201856(11):22-25,29.

基金

重庆市教委科学技术资助项目(KJQN202300117)
重庆市沙坪坝区技术创新与应用发展资助项目(2023116)

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