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

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.

Ultrahigh‐performance liquid chromatography–high‐resolution mass spectrometry‐based plasma metabolomics study of thymoma and thymic hyperplasia

“…IPA was significantly downregulated in class 1 (20 thymoma and 1 TC) compared with class 2 (12 thymic hyperplasia) ( p < 0.05, Figure 5A). Thymoma is often associated with autoimmune diseases, especially MG 20 . Studies have shown that 10–20% of MG patients develop thymoma and ca 30% of thymoma is associated with MG 22 .…”

“…Thymoma is often associated with autoimmune diseases, especially MG. 20 Studies have shown that 10-20% of MG patients develop thymoma and ca 30% of thymoma is associated with MG. 22 To investigate if the identified differential metabolic features had significant abundance changes between thymoma with and without MG, we analyzed their normalized abundance in TAMG (n = 10) and thymoma and 1 TC without MG (n = 11) samples. Tryptophan level in the TAMG group was found to be significantly lower than that in the MG(À) thymoma and TC group (Figure 5B), whereas the 9-decenoylcarnitine level was significantly higher (Figure 5C) (p < 0.05).…”

“…20 The authors mostly focused on the proteome changes and pathogenesis related to TAMG and MG(À) thymoma, and found that genes such as KRT1, GSN and COL6A1 were associated with TAMG(+) and that sphingolipid signaling pathway, glycerophospholipid metabolism, choline metabolism, fatty acid degradation and histidine metabolism were altered in TAMG and MG(À) thymoma compared with controls. 20 To our knowledge, there are currently no research reports on plasma differential metabolites between thymoma and thymic hyperplasia. In the work reported here, we conducted a metabolomics study of plasma samples of thymoma and thymic hyperplasia.…”

“…Tong et al carried out a comprehensive proteomics and metabolomics study of serum samples from 70 thymoma‐associated myasthenia gravis (TAMG), 62 thymoma without myasthenia gravis (MG; MG(−)) and 159 healthy controls 20 . The authors mostly focused on the proteome changes and pathogenesis related to TAMG and MG(−) thymoma, and found that genes such as KRT1, GSN and COL6A1 were associated with TAMG(+) and that sphingolipid signaling pathway, glycerophospholipid metabolism, choline metabolism, fatty acid degradation and histidine metabolism were altered in TAMG and MG(−) thymoma compared with controls 20 . To our knowledge, there are currently no research reports on plasma differential metabolites between thymoma and thymic hyperplasia.…”

“…Plasma and serum metabolomics could reflect systematic metabolic changes in the body, 19 which may provide valuable information for abnormalities of metabolism associated with thymomas. Tong et al carried out a comprehensive proteomics and metabolomics study of serum samples from 70 thymoma‐associated myasthenia gravis (TAMG), 62 thymoma without myasthenia gravis (MG; MG(−)) and 159 healthy controls 20 . The authors mostly focused on the proteome changes and pathogenesis related to TAMG and MG(−) thymoma, and found that genes such as KRT1, GSN and COL6A1 were associated with TAMG(+) and that sphingolipid signaling pathway, glycerophospholipid metabolism, choline metabolism, fatty acid degradation and histidine metabolism were altered in TAMG and MG(−) thymoma compared with controls 20 .…”