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Molecular network study of pituitary adenomas

Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Endocrinol. | doi: 10.3389/fendo.2018.00678

Integration of proteomics and metabolomics revealed metabolite-protein networks in ACTH- pituitary adenoma

 Jie Feng1, Qi Zhang2, Yang Zhou3, Shengyuan Yu1, Lichuan Hong1, 4, Sida Zhao1, Jingjing Yang1, 4, Hong Wan1,  Guowang Xu3, Yazhuo Zhang1 and  CHUZHONG LI1, 4*
  • 1Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, China
  • 2Second Affiliated Hospital, Zhejiang University School of Medicine, China
  • 3Dalian Institute of Chemical Physics (CAS), China
  • 4Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, China

Although surgery is a treatment option, an effective treatment with satisfying management of ACTH-PAs is currently lacking. We integrate the information obtained from the metabolomic and proteomic levels to identify critical networks and signaling pathways that may play important roles in metabolic regulation of ACTH-PAs and therefore hope to represent potential therapeutic targets.
Six ACTH-PAs and seven normal pituitary glands was performed Gas chromatography-mass spectrometry (GC-MS) analysis for metabolomics. Fiv eACTH-PAs and five normal pituitary glands were used for proteomics analysis by nano liquid chromatography tandem-mass spectrometry (nanoLC-MS/MS). The joint pathway analysis and network analysis was performed by MetaboAnalyst 3.0
There were significant differences of metabolites and proteins in the expression between ACTH-PAs and normal pituitary glands. A proteomic analysis identified 417 differentially expressed proteins which were significantly enriched in Myc signaling pathway. Protein-metabolite joint pathway analysis showed differential expressed proteins and metabolites was significantly enriched Glycolysis/Gluconeogenesis, Pyruvate metabolism, Citrate cycle (TCA cycle) and Fatty acid metabolism pathway in ACTH-PAs. The protein-metabolite molecular interaction network from the metabolites and proteins identified from metabolomics and proteomics created four subnetworks. Ten nodes in subnetwork 1 were the most significantly enriched in cell amino acid metabolism and pyrimidine nucleotide metabolism. Additionally, 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 pathway networks that function in ACTH-PAs. Our results demonstrated downregulated glycolysis and fatty acid synthesis in this tumor. We also revealed that Myc signaling pathway significantly participated in metabolic change and tumorigenesis of ACTH-PAs. Those data may provide biomarkers for ACTH-PA diagnosis and monitoring, and also possibly lead to the development of novel strategies to treat pituitary adenomas.

Keywords: Metabolite-protein networks, Proteomics, Metabolomics, ACTH, pituitary adenoma

Received: 22 Jun 2018; Accepted: 29 Oct 2018.

Edited by:

Xianquan Zhan, Xiangya Hospital, Central South University, China

Reviewed by:

Odelia Cooper, Cedars-Sinai Medical Center, United States
Jianbo Pan, Johns Hopkins Medicine, United States  

Copyright: © 2018 Feng, Zhang, Zhou, Yu, Hong, Zhao, Yang, Wan, Xu, Zhang and LI. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. CHUZHONG LI, Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, Beijing, China, lichuzhong@163.com