Biological Trace Element Research

, Volume 183, Issue 1, pp 40–48 | Cite as

Network Analysis of Se-and Zn-related Proteins in the Serum Proteomics Expression Profile of the Endemic Dilated Cardiomyopathy Keshan Disease

  • Sen Wang
  • Yanyan Lv
  • Yingting Wang
  • Peiru Du
  • Wuhong Tan
  • Mikko J. Lammi
  • Xiong Guo


Keshan disease (KD) is an endemic cardiomyopathy with high mortality. Selenium (Se) and zinc (Zn) deficiencies are closely related to KD. The molecular mechanism of KD pathogenesis is still unclear. There are only few studies on the interaction of trace elements and proteins associated with the pathogenesis of KD. In this study, isobaric tags for relative and absolute quantitation (iTRAQ)-coupled two-dimensional liquid chromatography tandem mass spectrometry (2DLC-MS/MS) technique analysis was used to analyze the differential expression of proteins from serum samples. Comparative Toxicogenomics Database (CTD) was used to screen Se- and Zn-associated proteins. Then, pathway and network analyses of Se- and Zn-associated proteins were constituted by Cytoscape ClueGO and GeneMANIA plugins. One hundred and five differentially expressed proteins were obtained by 2DLC-MS/MS, among them 19 Se- and 3 Zn-associated proteins. Fifty-two pathways were identified from ClueGO and 1 network from GeneMANIA analyses. The results showed that Se-associated proteins STAT3 and MAPK1 and Zn-associated proteins HIF1A and PARP1, the proteins involved in HIF-1 signaling pathway and apoptosis pathway, may play significant roles in the pathogenesis of KD. The approach of this study would be also beneficial for further dissecting molecular mechanism of other trace element-associated disease.


iTRAQ Trace element Keshan disease Cardiomyocyte GeneGO GeneMANIA 



This study was supported by the National Natural Science Foundation of China (grant numbers 81273008 and 81402638).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflicts of interest.

Supplementary material

12011_2017_1063_MOESM1_ESM.docx (24 kb)
Table S1 (DOCX 24 kb)


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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  1. 1.School of Public HealthHealth Science Center of Xi’an Jiaotong UniversityShaanxiChina
  2. 2.Key Laboratory of Trace Elements and Endemic DiseasesNational Health and Family Planning CommissionShaanxiChina
  3. 3.Department of RheumatologyXi’an No.5 HospitalShaanxiChina
  4. 4.Department of Integrative Medical BiologyUniversity of UmeåUmeåSweden

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