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Liquid chromatography-mass spectrometry based metabolic characterization of pleural effusion in patients with acquired EGFR-TKI resistance

文献类型：期刊论文

作者Li, Na1,2,3; Mao, Weimin2,3; Gao, Yun2,3; Wang, Ding1,2,3; Song, Zhengbo2,3; Chen, Zhongjian2,3
刊名JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
出版日期2021-08-05
卷号202
关键词Lung cancer EGFR-TKI Resistance Pleural effusion Metabolomics Biomarker
ISSN号0731-7085
DOI10.1016/j.jpba.2021.114147
通讯作者Song, Zhengbo(songzb@zjcc.org.cn) ; Chen, Zhongjian(chenzj@zjcc.org.cn)
英文摘要Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) acquired resistance remains a major barrier in the clinical treatment of lung adenocarcinoma with epidermal growth factor recep-tor (EGFR) mutations. Despite extensive efforts, mechanism of acquired resistance has not yet been elucidated clearly. The subject of this study was to characterize the metabolic signatures relevant to acquired EGFR-TKI resistance in pleural effusion (PE), and identify potential biomarkers in PE of patients with acquired EGFR-TKI resistance. PE from EGFR-TKI untreated group (n = 30) and EGFR-TKI resistant group (n = 18) was analyzed using liquid chromatography-mass spectrometry (LC MS) based metabolomic. Multivariate statistical analysis revealed distinctive diff ;erences between the groups. A total of 34 significantly differential metabolites in PE were identified, among which, the acquired EGFR-TKI resistant group had higher levels of L-lysine, taurine, ornithine and citrulline, and lower levels of L-tryptophan, kynurenine, L-phenylalanine, L-leucine, N-formyl-L-methionine, 3-hydroxyphenylacetic acid and N-acetyl-d-phenylalanine in PE than that of the EGFR-TKI untreated group. These metabo-lites are mainly involved in six amino acid metabolic pathways. In addition, 3-hydroxyphenylacetic acid and N-acetyl-d-phenylalanine showed the highest AUC values of 0.934 and 0.929 in receiver operating characteristic analysis. Through LC MS metabolomics, our study identified potential biomarkers in PE, differentiating EGFR-TKI resistant patients from untreated patients, as well as the mechanisms underlying acquired EGFR-TKI resistance; thus, providing novel insights into acquired EGFR-TKI resistance. (C) 2021 Elsevier B.V. All rights reserved.
WOS关键词CANCER ; TYROSINE ; PROFILE ; TISSUE ; SERUM
资助项目Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital) ; National Natural Science Foundation of China[81672315] ; Key R&D Program Projects in Zhejiang Province[2017C04G1360498] ; Special Foundation for Young Scientists Science and Technology Program of Tradition Chinese Medicine of Zhejiang Province[2017ZQ007]
WOS研究方向Chemistry ; Pharmacology & Pharmacy
语种英语
WOS记录号WOS:000659231300006
出版者ELSEVIER
资助机构Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital) ; National Natural Science Foundation of China ; Key R&D Program Projects in Zhejiang Province ; Special Foundation for Young Scientists Science and Technology Program of Tradition Chinese Medicine of Zhejiang Province
源URL[http://ir.hfcas.ac.cn:8080/handle/334002/123902]  
专题中国科学院合肥物质科学研究院
通讯作者Song, Zhengbo; Chen, Zhongjian
作者单位1.Zhejiang Chinese Med Univ, Clin Med Coll 2, Hangzhou 310053, Zhejiang, Peoples R China
2.Univ Chinese Acad Sci, Zhejiang Canc Hosp, Canc Hosp, Hangzhou, Zhejiang, Peoples R China
3.Chinese Acad Sci, Inst Canc & Basic Med ICBM, Hangzhou 310022, Zhejiang, Peoples R China
推荐引用方式
GB/T 7714		 Li, Na,Mao, Weimin,Gao, Yun,et al. Liquid chromatography-mass spectrometry based metabolic characterization of pleural effusion in patients with acquired EGFR-TKI resistance[J]. JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS,2021,202.
APA Li, Na,Mao, Weimin,Gao, Yun,Wang, Ding,Song, Zhengbo,&Chen, Zhongjian.(2021).Liquid chromatography-mass spectrometry based metabolic characterization of pleural effusion in patients with acquired EGFR-TKI resistance.JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS,202.
MLA Li, Na,et al."Liquid chromatography-mass spectrometry based metabolic characterization of pleural effusion in patients with acquired EGFR-TKI resistance".JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS 202(2021).

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来源：合肥物质科学研究院

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