Clinically, thymoma patients are often complicated with myasthenia gravis (MG). Dexamethasone, a glucocorticoid with anti-inflammatory effects, could be used as an immunosuppressant for thymoma-associated MG, but the mechanism of action remains to be explored. In this study, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, weighted gene co-expression network analysis (WGCNA) of potential targets was performed by screening the intersection targets of dexamethasone and thymoma-associated MG from the database. Furthermore, the key targets and core active components were identified by topological analysis of the protein-protein interaction (PPI) network. Molecular docking technology was applied to screen the complexes with stable binding of dexamethasone and core targets. Patients with thymoma were divided into two groups according to whether they received dexamethasone before operation, and immunohistochemistry and western blot were used to verify the selected target of dexamethasone in treating thymoma-associated MG. The results showed that the action pathway of dexamethasone on the disease was closely enriched to phosphatidylinositol 3-kinase (PI3K)-protein kinase B (PKB/AKT), mammalian target of rapamycin (mTOR) signaling pathways. The expressions of AKT1 and its downstream molecule mTOR in the thymoma microenvironment of thymoma-associated MG patients who did not receive dexamethasone before operation were higher than those in the group receiving dexamethasone before operation. This study demonstrates that dexamethasone can promote apoptosis through the AKT-mTOR pathway for the treatment of thymoma-associated MG, as validated by network pharmacology predictions and clinical specimen experiments, and can be verified by large-scale clinical trials in the future. This study also provides theoretical support and new research perspectives for this disease.
Keywords: Dexamethasone; Molecular docking; Myasthenia gravis; Network pharmacology; Thymoma.
© 2023. The Author(s).