Combination of GC-MS based metabolomics analysis with mouse xenograft models reveals a panel of dysregulated circulating metabolites and potential therapeutic targets for colorectal cancer

doi:10.21037/tcr-20-3406

	Combination of GC-MS based metabolomics analysis with mouse xenograft models reveals a panel of dysregulated circulating metabolites and potential therapeutic targets for colorectal cancer
	Ni, Juan 1,2,4; Chen, Yang 3; Li, Ningning 1,2,4; Sun, Diandian 1,2,4; Ju, Haixing 1,2,4; Chen, Zhongjian 1,2,4
刊名	TRANSLATIONAL CANCER RESEARCH
	2021-04-01
卷号	10
关键词	Gas chromatography-mass spectrometry (GC-MS) metabolomics colorectal cancer (CRC) amino acid transporter
ISSN号	2218-676X
DOI	10.21037/tcr-20-3406
通讯作者	Ju, Haixing(juhx@zjcc.org.cn) ; Chen, Zhongjian(chenzj@zjcc.org.cn)
英文摘要	Background: Colorectal cancer (CRC) is a common gastrointestinal tumor with subtle, often undetectable early symptoms, which means that upon diagnosis, patients often present in the middle or late stages of disease. Therefore, the need for an effective biomarker for the early diagnosis and development of novel therapeutic targets is urgent to prolong patient survival time and reduce mortality. Methods: Twenty mice were randomly divided into patient-derived xenograft (PDX) model (transplantation of fresh CRC tumor samples) and control groups (10 mice in each group). All the animals were euthanized using isoflurane at the end of the experiment. Gas chromatography-mass spectrometry (GC-MS)-based metabolomic profiling was performed to investigate the differential metabolites in the serum, and publicly available gene expression data (GSE106582) were analyzed to determine dysregulated metabolic pathways. Joint pathway analysis was used to identify potential metabolic targets. Immunohistochemistry analysis was performed to confirm the presence of the identified targets at the protein level. Results: A total of 96 differential circulating metabolites were identified, which were predominantly involved in amino acid metabolism. In particular, the serum levels of amino acids such as phenylalanine and aspartic acid were significantly downregulated in the PDX group, suggesting an increased consumption of amino acids in CRC. Moreover, both the mRNA and protein levels of the amino acid transporters, SLC7A5 and SLC1A5, were found to be upregulated in CRC. Conclusions: By combining GC-MS-based metabolomics profiling with a PDX model of CRC our study successfully identified potential diagnostic circulating metabolites. Dysregulated amino acid metabolism was found to be a significant feature of CRC. The amino acid transporters, SLC7A5 and SLC1A5, were identified as potential metabolic therapeutic targets. This study furthers the understanding of the metabolic processes involved in CRC.
资助项目	Zhejiang Science and Technology Project for Medicine[2020RC004]
WOS关键词	CHROMATOGRAPHY-MASS SPECTROMETRY ; AMINO-ACID ; METHIONINE ; SURVIVAL ; GROWTH ; CELLS ; GAS
WOS研究方向	Oncology
语种	英语
出版者	AME PUBL CO
WOS记录号	WOS:000646069200018
资助机构	Zhejiang Science and Technology Project for Medicine
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/122257]
专题	中国科学院合肥物质科学研究院
通讯作者	Ju, Haixing; Chen, Zhongjian
作者单位	1.Chinese Acad Sci, Inst Canc & Basic Med IBMC, Hangzhou 310022, Peoples R China 2.Zhejiang Canc Hosp, Expt Res Ctr, Hangzhou 310022, Peoples R China 3.Zhejiang Univ, Coll Pharmaceut Sci, Hangzhou, Peoples R China 4.Univ Chinese Acad Sci, Zhejiang Canc Hosp, Canc Hosp, Hangzhou 310022, Peoples R China
推荐引用方式 GB/T 7714	Ni, Juan,Chen, Yang,Li, Ningning,et al. Combination of GC-MS based metabolomics analysis with mouse xenograft models reveals a panel of dysregulated circulating metabolites and potential therapeutic targets for colorectal cancer[J]. TRANSLATIONAL CANCER RESEARCH,2021,10.
APA	Ni, Juan,Chen, Yang,Li, Ningning,Sun, Diandian,Ju, Haixing,&Chen, Zhongjian.(2021).Combination of GC-MS based metabolomics analysis with mouse xenograft models reveals a panel of dysregulated circulating metabolites and potential therapeutic targets for colorectal cancer.TRANSLATIONAL CANCER RESEARCH,10.
MLA	Ni, Juan,et al."Combination of GC-MS based metabolomics analysis with mouse xenograft models reveals a panel of dysregulated circulating metabolites and potential therapeutic targets for colorectal cancer".TRANSLATIONAL CANCER RESEARCH 10(2021).