Metabolomics of a cell line-derived xenograft model reveals circulating metabolic signatures for malignant mesothelioma

doi:10.7717/peerj.12568

	Metabolomics of a cell line-derived xenograft model reveals circulating metabolic signatures for malignant mesothelioma
	Gao, Yun 1,2,3; Dai, Ziyi 1,2; Yang, Chenxi 1,2; Wang, Ding 1,2,4; Guo, Zhenying 1,2; Mao, Weimin 1,2,3; Chen, Zhongjian 1,2,3
刊名	PEERJ
	2022-01-04
卷号	9
关键词	Cell line-derived xenograft GC-MS Malignant mesothelioma Metabolomics Amino acid metabolism
ISSN号	2167-8359
DOI	10.7717/peerj.12568
通讯作者	Mao, Weimin(maowm@zjcc.org.cn) ; Chen, Zhongjian(chenzj@zjcc.org.cn)
英文摘要	Background. Malignant mesothelioma (MM) is a rare and highly aggressive cancer. Despite advances in multidisciplinary treatments for cancer, the prognosis for MM remains poor with no effective diagnostic biomarkers currently available. The aim of this study was to identify plasma metabolic biomarkers for better MM diagnosis and prognosis by use of a MM cell line-derived xenograft (CDX) model. Methods. The MM CDX model was confirmed by hematoxylin and eosin staining and immunohistochemistry. Twenty female nude mice were randomly divided into two groups, 10 for theMMCDX model and 10 controls. Plasma samples were collected two weeks after tumor cell implantation. Gas chromatography-mass spectrometry analysis was conducted. Both univariate and multivariate statistics were used to select potential metabolic biomarkers. Hierarchical clustering analysis, metabolic pathway analysis, and receiver operating characteristic (ROC) analysis were performed. Additionally, bioinformatics analysis was used to investigate differential genes between tumor and normal tissues, and survival-associated genes. Results. The MM CDX model was successfully established. With VIP > 1.0 and Pvalue < 0.05, a total of 23 differential metabolites were annotated, in which isoleucine, 5-dihydrocortisol, and indole-3-acetamide had the highest diagnostic values based on ROC analysis. These were mainly enriched in pathways for starch and sucrose metabolism, pentose and glucuronate interconversions, galactose metabolism, steroid hormone biosynthesis, as well as phenylalanine, tyrosine and tryptophan biosynthesis. Further, down-regulation was observed for amino acids, especially isoleucine, which is consistent with up-regulation of amino acid transporter genes SLC7A5 and SLC1A3 in MM.Overall survival was also negatively associated with SLC1A5, SLC7A5, and SLC1A3. Conclusion. We found several altered plasma metabolites in the MM CDX model. The importance of specific metabolic pathways, for example amino acid metabolism, is herein highlighted, although further investigation is warranted.
资助项目	Institutional Animal Care and Ethics Committee of Zhejiang Cancer Hospital[2019-02-010]
WOS关键词	AMINO-ACID-METABOLISM ; CANCER
WOS研究方向	Science & Technology - Other Topics
语种	英语
出版者	PEERJ INC
WOS记录号	WOS:000741766000001
资助机构	Institutional Animal Care and Ethics Committee of Zhejiang Cancer Hospital
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/127129]
专题	中国科学院合肥物质科学研究院
通讯作者	Mao, Weimin; Chen, Zhongjian
作者单位	1.Chinese Acad Sci, Inst Basic Med & Canc IBMC, Hangzhou, Peoples R China 2.Univ Chinese Acad Sci, Canc Hosp, Zhejiang Canc Hosp, Hangzhou, Peoples R China 3.Zhejiang Key Lab Diag & Treatment Technol Thoraci, Hangzhou, Peoples R China 4.Zhejiang Chinese Med Univ, Hangzhou, Peoples R China
推荐引用方式 GB/T 7714	Gao, Yun,Dai, Ziyi,Yang, Chenxi,et al. Metabolomics of a cell line-derived xenograft model reveals circulating metabolic signatures for malignant mesothelioma[J]. PEERJ,2022,9.
APA	Gao, Yun.,Dai, Ziyi.,Yang, Chenxi.,Wang, Ding.,Guo, Zhenying.,...&Chen, Zhongjian.(2022).Metabolomics of a cell line-derived xenograft model reveals circulating metabolic signatures for malignant mesothelioma.PEERJ,9.
MLA	Gao, Yun,et al."Metabolomics of a cell line-derived xenograft model reveals circulating metabolic signatures for malignant mesothelioma".PEERJ 9(2022).