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

PeerJ

article

Yun Gao¹  Ziyi Dai¹  Chenxi Yang¹  Ding Wang¹  Zhenying Guo¹  Weimin Mao¹  Zhongjian Chen¹ 

[1]The Cancer Hospital of the University of Chinese Academy of Sciences ,(Zhejiang Cancer Hospital)

[2]Institute of Basic Medicine and Cancer ,(IBMC), Chinese Academy of Sciences

[3]Zhejiang Key Laboratory of Diagnosis&Treatment Technology on Thoracic Oncology

[4]Zhejiang Chinese Medical University

关键词: Cell line-derived xenograft;    GC-MS;    Malignant mesothelioma;    Metabolomics;    Amino acid metabolism;   

DOI  :  10.7717/peerj.12568

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

BackgroundMalignant 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.MethodsThe MM CDX model was confirmed by hematoxylin and eosin staining and immunohistochemistry. Twenty female nude mice were randomly divided into two groups, 10 for the MM CDX 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.Results1.0 and P-value < 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.ConclusionWe 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.

【 授权许可】

CC BY