Integration of Proteomics and Metabolomics Revealed Metabolite-Protein Networks in ACTH-Secreting Pituitary Adenoma

doi:10.3389/fendo.2018.00678

	Integration of Proteomics and Metabolomics Revealed Metabolite-Protein Networks in ACTH-Secreting Pituitary Adenoma
	Hong, Lichuan 1; Feng, Jie 1,2,3; Zhang, Qi 4; Zhou, Yang 5; Yu, Shenyuan 1; Zhao, Sida 1; Yang, Jingjing 1; Wan, Hong 1; Xu, Guowang 5; Zhang, Yazhuo 1,2,3
刊名	FRONTIERS IN ENDOCRINOLOGY
	2018-11-23
卷号	9 页码:13
关键词	metabolite-protein networks proteomics metabolomics ACTH pituitary adenoma
ISSN号	1664-2392
DOI	10.3389/fendo.2018.00678
通讯作者	Li, Chuzhong(lichuzhong@163.com)
英文摘要	An effective treatment for the management of adrenocorticotropic hormone-secreting pituitary adenomas (ACTH-PA) is currently lacking, although surgery is a treatment option. We have integrated information obtained at the metabolomic and proteomic levels to identify critical networks and signaling pathways that may play important roles in the metabolic regulation of ACTH-PA and therefore hopefully represent potential therapeutic targets. Six ACTH-PAs and seven normal pituitary glands were investigated via gas chromatography-mass spectrometry (GC-MS) analysis for metabolomics. Five ACTH-PAs and five normal pituitary glands were subjected to proteomics analysis via nano liquid chromatography tandem-mass spectrometry (nanoLC-MS/MS). The joint pathway analysis and network analysis was performed using MetaboAnalyst 3.0. software. There were significant differences of metabolites and protein expression levels between the ACTH-PAs and normal pituitary glands. A proteomic analysis identified 417 differentially expressed proteins that were significantly enriched in the Myc signaling pathway. The protein-metabolite joint pathway analysis showed that differentially expressed proteins and metabolites were significantly enriched in glycolysis/gluconeogenesis, pyruvate metabolism, citrate cycle (ICA cycle), and the fatty acid metabolism pathway in ACTH-PA. The protein-metabolite molecular interaction network identified from the metabolomics and proteomics investigation resulted in four subnetworks. Ten nodes in subnetwork 1 were the most significantly enriched in cell amino acid metabolism and pyrimidine nucleotide metabolism. Additionally, the metabolite-gene-disease interaction network established nine subnetworks. Ninety-two nodes in subnetwork 1 were the most significantly enriched in carboxylic acid metabolism and organic acid metabolism. The present study clarified the pathway networks that function in ACTH-PA. Our results demonstrated the presence of downregulated glycolysis and fatty acid synthesis in this tumor type. We also revealed that the Myc signaling pathway significantly participated in the metabolic changes and tumorigenesis of ACTH-PA. This data may provide biomarkers for ACTH-PA diagnosis and monitoring, and could also lead to the development of novel strategies for treating pituitary adenomas.
资助项目	Research Special Fund for Public Welfare Industry of Health[201402008] ; National High Technology Research and Development Program of China[2014AA020610] ; Beijing Municipal Administration of Hospitals Youth Program[QML20160506] ; National Natural Science Foundation of China[81702455]
WOS关键词	ACTIVATION ; PATHWAY ; ROLES ; MYC ; P53
WOS研究方向	Endocrinology & Metabolism
语种	英语
出版者	FRONTIERS MEDIA SA
WOS记录号	WOS:000451089100001
资助机构	Research Special Fund for Public Welfare Industry of Health ; Research Special Fund for Public Welfare Industry of Health ; National High Technology Research and Development Program of China ; National High Technology Research and Development Program of China ; Beijing Municipal Administration of Hospitals Youth Program ; Beijing Municipal Administration of Hospitals Youth Program ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; Research Special Fund for Public Welfare Industry of Health ; Research Special Fund for Public Welfare Industry of Health ; National High Technology Research and Development Program of China ; National High Technology Research and Development Program of China ; Beijing Municipal Administration of Hospitals Youth Program ; Beijing Municipal Administration of Hospitals Youth Program ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; Research Special Fund for Public Welfare Industry of Health ; Research Special Fund for Public Welfare Industry of Health ; National High Technology Research and Development Program of China ; National High Technology Research and Development Program of China ; Beijing Municipal Administration of Hospitals Youth Program ; Beijing Municipal Administration of Hospitals Youth Program ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; Research Special Fund for Public Welfare Industry of Health ; Research Special Fund for Public Welfare Industry of Health ; National High Technology Research and Development Program of China ; National High Technology Research and Development Program of China ; Beijing Municipal Administration of Hospitals Youth Program ; Beijing Municipal Administration of Hospitals Youth Program ; National Natural Science Foundation of China ; National Natural Science Foundation of China
内容类型	期刊论文
源URL	[http://cas-ir.dicp.ac.cn/handle/321008/166540]
专题	大连化学物理研究所_中国科学院大连化学物理研究所
通讯作者	Li, Chuzhong
作者单位	1.Capital Med Univ, Beijing Neurosurg Inst, Beijing Tiantan Hosp, Beijing, Peoples R China 2.Capital Med Univ, Beijing Inst Brain Disorders, Brain Tumor Ctr, Beijing, Peoples R China 3.Capital Med Univ, Beijing Tiantan Hosp, China Natl Clin Res Ctr Neurol Dis, Beijing, Peoples R China 4.Zhejiang Univ, Affiliated Hosp 2, Dept Hepatobiliary & Pancreat Surg, Sch Med, Hangzhou, Zhejiang, Peoples R China 5.Chinese Acad Sci, Dalian Inst Chem Phys, CAS Key Lab Separat Sci Analyt Chem, Dalian, Peoples R China
推荐引用方式 GB/T 7714	Hong, Lichuan,Feng, Jie,Zhang, Qi,et al. Integration of Proteomics and Metabolomics Revealed Metabolite-Protein Networks in ACTH-Secreting Pituitary Adenoma[J]. FRONTIERS IN ENDOCRINOLOGY,2018,9:13.
APA	Hong, Lichuan.,Feng, Jie.,Zhang, Qi.,Zhou, Yang.,Yu, Shenyuan.,...&Li, Chuzhong.(2018).Integration of Proteomics and Metabolomics Revealed Metabolite-Protein Networks in ACTH-Secreting Pituitary Adenoma.FRONTIERS IN ENDOCRINOLOGY,9,13.
MLA	Hong, Lichuan,et al."Integration of Proteomics and Metabolomics Revealed Metabolite-Protein Networks in ACTH-Secreting Pituitary Adenoma".FRONTIERS IN ENDOCRINOLOGY 9(2018):13.