机构：[1]Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, Beijing, China,研究所北京市神经外科研究所首都医科大学附属天坛医院[2]Beijing Institute for Brain Disorders, Brain Tumor Center, Capital Medical University, Beijing, China,[3]China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China,重点科室诊疗科室神经病学中心神经病学中心首都医科大学附属天坛医院[4]Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China,[5]CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China
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.
基金：
Research Special Fund for Public Welfare Industry of Health [201402008]; National High Technology Research and Development Program of ChinaNational High Technology Research and Development Program of China [2014AA020610]; Beijing Municipal Administration of Hospitals Youth Program [QML20160506]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81702455]
第一作者机构：[1]Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, Beijing, China,[2]Beijing Institute for Brain Disorders, Brain Tumor Center, Capital Medical University, Beijing, China,[3]China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China,
共同第一作者：
通讯作者：
通讯机构：[1]Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, Beijing, China,[2]Beijing Institute for Brain Disorders, Brain Tumor Center, Capital Medical University, Beijing, China,[3]China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China,
推荐引用方式(GB/T 7714)：
Feng Jie,Zhang Qi,Zhou Yang,et al.Integration of Proteomics and Metabolomics Revealed Metabolite-Protein Networks in ACTH-Secreting Pituitary Adenoma[J].FRONTIERS IN ENDOCRINOLOGY.2018,9:-.doi:10.3389/fendo.2018.00678.
APA：
Feng, Jie,Zhang, Qi,Zhou, Yang,Yu, Shenyuan,Hong, Lichuan...&Li, Chuzhong.(2018).Integration of Proteomics and Metabolomics Revealed Metabolite-Protein Networks in ACTH-Secreting Pituitary Adenoma.FRONTIERS IN ENDOCRINOLOGY,9,
MLA：
Feng, Jie,et al."Integration of Proteomics and Metabolomics Revealed Metabolite-Protein Networks in ACTH-Secreting Pituitary Adenoma".FRONTIERS IN ENDOCRINOLOGY 9.(2018):-
