Combined Metabolomic Analysis of Plasma and Tissue Reveals a Prognostic Risk Score System and Metabolic Dysregulation in Esophageal Squamous Cell Carcinoma

doi:10.3389/fonc.2020.01545

	Combined Metabolomic Analysis of Plasma and Tissue Reveals a Prognostic Risk Score System and Metabolic Dysregulation in Esophageal Squamous Cell Carcinoma
	Chen, Zhongjian 1,2,3,4; Dai, Yalan 1,3,4; Huang, Xiancong 1,3,4; Chen, Keke 1,3,4,5; Gao, Yun 1,3,4; Li, Na 1,3,4; Wang, Ding 1,3,4; Chen, Aiping 1,3,4; Yang, Qingxia 2; Hong, Yanjun 6
刊名	FRONTIERS IN ONCOLOGY
	2020-08-26
卷号	10
关键词	esophageal squamous cell carcinoma (ESCC) metabolomics risk score prognosis diagnosis indoleamine 2 3-dioxygenase 1 (IDO1) artificial intelligence
ISSN号	2234-943X
DOI	10.3389/fonc.2020.01545
通讯作者	Zeng, Su(zengsu@zju.edu.cn) ; Mao, Weimin(maowm1218@163.com)
英文摘要	Background:Esophageal squamous cell carcinoma (ESCC) is a gastrointestinal malignancy with a poor prognosis. Although studies have shown metabolic reprogramming to be linked to ESCC development, no prognostic metabolic biomarkers or potential therapeutic metabolic targets have been identified. Method:The present study investigated some circulating metabolites associated with overall survival in 276 curatively resected ESCC patients using liquid chromatography/mass spectrometry metabolomics and Kaplan-Meier analysis. Tissue metabolomic analysis of 23-paired ESCC tissue samples was performed to discover metabolic dysregulation in ESCC cancerous tissue. A method consisting of support vector machine recursive feature elimination and LIMMA differential expression analysis was utilized to select promising feature genes within transcriptomic data from 179-paired ESCC tissue samples. Joint pathway analysis with genes and metabolites identified relevant metabolic pathways and targets for ESCC. Results:Four metabolites, kynurenine, 1-myristoyl-glycero-3-phosphocholine (LPC(14:0)sn-1), 2-piperidinone, and hippuric acid, were identified as prognostic factors in the preoperative plasma from ESCC patients. A risk score consisting of kynurenine and LPC(14:0)sn-1 significantly improved the prognostic performance of the tumor-node-metastasis staging system and was able to stratify risk for ESCC. Combined tissue metabolomic analysis and support vector machine recursive feature elimination gene selection revealed dysregulated kynurenine pathway as an important metabolic feature of ESCC, including accumulation of tryptophan, formylkynurenine, and kynurenine, as well as up-regulated indoleamine 2,3-dioxygenase 1 in ESCC cancerous tissue. Conclusions:This work identified for the first time four potential prognostic circulating metabolites. In addition, kynurenine pathway metabolism was shown to be up-regulated tryptophan-kynurenine metabolism in ESCC. Results not only provide a metabolite-based risk score system for prognosis, but also improve the understanding of the molecular basis of ESCC onset and progression, and as well as novel potential therapeutic targets for ESCC.
资助项目	National Natural Science Foundation of China[81672315] ; National Natural Science Foundation of China[81302840] ; National Natural Science Foundation of China[81802472] ; Zhejiang Provincial Natural Science Foundation of China[LQ18H160020] ; 1022 Talent Training Program of Zhejiang Cancer Hospital ; Science, Technology and Innovation Commission of Shenzhen[JCYJ20160531193901593] ; Hong Kong Baptist University, Faculty Research Grants[2/17-18/088] ; Leading Talent of Ten Thousand Plan-National High-Level Talents Special Support Plan
WOS关键词	CANCER STATISTICS ; PROGRESSION ; KYNURENINE ; BIOMARKERS ; SURVIVAL ; TRENDS ; IDO1
WOS研究方向	Oncology
语种	英语
出版者	FRONTIERS MEDIA SA
WOS记录号	WOS:000570473200001
资助机构	National Natural Science Foundation of China ; Zhejiang Provincial Natural Science Foundation of China ; 1022 Talent Training Program of Zhejiang Cancer Hospital ; Science, Technology and Innovation Commission of Shenzhen ; Hong Kong Baptist University, Faculty Research Grants ; Leading Talent of Ten Thousand Plan-National High-Level Talents Special Support Plan
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/104290]
专题	中国科学院合肥物质科学研究院
通讯作者	Zeng, Su; Mao, Weimin
作者单位	1.Univ Chinese Acad Sci, Canc Hosp, Hangzhou, Peoples R China 2.Zhejiang Univ, Coll Pharmaceut Sci, Hangzhou, Peoples R China 3.Chinese Acad Sci, Inst Canc & Basic Med ICBM, Hangzhou, Peoples R China 4.Zhejiang Canc Hosp, Hangzhou, Peoples R China 5.Imperial Coll London, Sch Med, London, England 6.Hong Kong Baptist Univ, Dept Chem, Hong Kong, Peoples R China
推荐引用方式 GB/T 7714	Chen, Zhongjian,Dai, Yalan,Huang, Xiancong,et al. Combined Metabolomic Analysis of Plasma and Tissue Reveals a Prognostic Risk Score System and Metabolic Dysregulation in Esophageal Squamous Cell Carcinoma[J]. FRONTIERS IN ONCOLOGY,2020,10.
APA	Chen, Zhongjian.,Dai, Yalan.,Huang, Xiancong.,Chen, Keke.,Gao, Yun.,...&Mao, Weimin.(2020).Combined Metabolomic Analysis of Plasma and Tissue Reveals a Prognostic Risk Score System and Metabolic Dysregulation in Esophageal Squamous Cell Carcinoma.FRONTIERS IN ONCOLOGY,10.
MLA	Chen, Zhongjian,et al."Combined Metabolomic Analysis of Plasma and Tissue Reveals a Prognostic Risk Score System and Metabolic Dysregulation in Esophageal Squamous Cell Carcinoma".FRONTIERS IN ONCOLOGY 10(2020).