Identification of Potential Key Genes for the Comorbidity of Myasthenia Gravis With Thymoma by Integrated Bioinformatics Analysis and Machine Learning.

Abstract

Background: Thymoma is a key risk factor for myasthenia gravis (MG). The purpose of our study was to investigate the potential key genes responsible for MG patients with thymoma.

Methods: We obtained MG and thymoma dataset from GEO database. Differentially expressed genes (DEGs) were determined and functional enrichment analyses were conducted by R packages. Weighted gene co-expression network analysis (WGCNA) was used to screen out the crucial module genes related to thymoma. Candidate genes were obtained by integrating DEGs of MG and module genes. Subsequently, we identified several candidate key genes by machine learning for diagnosing MG patients with thymoma. The nomogram and receiver operating characteristics (ROC) curves were applied to assess the diagnostic value of candidate key genes. Finally, we investigated the infiltration of immunocytes and analyzed the relationship among key genes and immune cells.

Results: We obtained 337 DEGs in MG dataset and 2150 DEGs in thymoma dataset. Biological function analyses indicated that DEGs of MG and thymoma were enriched in many common pathways. Black module (containing 207 genes) analyzed by WGCNA was considered as the most correlated with thymoma. Then, 12 candidate genes were identified by intersecting with MG DEGs and thymoma module genes as potential causes of thymoma-associated MG pathogenesis. Furthermore, five candidate key genes (JAM3, MS4A4A, MS4A6A, EGR1, and FOS) were screened out through integrating least absolute shrinkage and selection operator (LASSO) regression and Random forest (RF). The nomogram and ROC curves (area under the curve from 0.833 to 0.929) suggested all five candidate key genes had high diagnostic values. Finally, we found that five key genes and immune cell infiltrations presented varying degrees of correlation.

Conclusions: Our study identified five key potential pathogenic genes that predisposed thymoma to the development of MG, which provided potential diagnostic biomarkers and promising therapeutic targets for MG patients with thymoma.