Integrated proteomics and metabolomics analysis reveals hubs protein and network alterations in myasthenia gravis

Aging (Albany NY). 2022 Jul 8;14(13):5417-5426. doi: 10.18632/aging.204156. Epub 2022 Jul 8.

Abstract

Background: Thymoma-associated myasthenia gravis (TAMG) is a well-described subtype of Myasthenia gravis (MG). Nevertheless, the detailed proteins and bioprocess differentiating TAMG from TAMG (-) thymoma have remained unclear.

Methods: The proteomics and metabolomics were carried out on serum samples from thymoma group (n = 60, TNMG), TAMG (+) thymoma group (n = 70, TAMG (+)), and TAMG (-) thymomas group (n = 62, TAMG (-)), and controls (n = 159). groups. Proteomics and metabolomics analyses, including weighted gene co-expression network analysis (WGCNA), was conducted to detect the hub proteins and metabolomics processes that could differentiate TAMG (+) from TAMG (-) thymomas. MetaboAnalyst was used to examine the integration of proteomic and metabolomic analysis to differentiate TAMG (+) from TAMG (-) thymomas.

Results: The of module-trait correlation of WGCNA analysis identified KRT1, GSN, COL6A1, KRT10, FOLR2, KRT9, KRT2, TPI1, ARF3, LYZ, ADIPOQ, SEMA4B, IGKV1-27, MASP2, IGF2R was associated with TAMG (+) thymomas. In addition, organismal systems-immune system and metabolism-biosynthesis of other secondary metabolites were closely related to the mechanism of TAMG (+) pathogenesis.

Conclusion: Our integrated proteomics and metabolomics analysis supply a systems-level view of proteome changes in TAMG (+), TAMG (-) thymomas and exposes disease-associated protein network alterations involved in.

Keywords: WGCNA; gene co-expression networks; metabolomics; myasthenia gravis; proteomics.

MeSH terms

  • Folate Receptor 2*
  • Humans
  • Mannose-Binding Protein-Associated Serine Proteases / metabolism
  • Metabolomics
  • Myasthenia Gravis* / genetics
  • Proteomics
  • Thymoma*
  • Thymus Neoplasms*

Substances

  • FOLR2 protein, human
  • Folate Receptor 2
  • MASP2 protein, human
  • Mannose-Binding Protein-Associated Serine Proteases