Abstract
Background: Approximately 50% of thymoma patients also show myasthenia gravis (MG), which is an autoimmune disease; however, the pathogenesis of MG-associated thymoma remains elusive. Our aim was to investigate immune-related lncRNA profiles of a set of candidate genes for better understanding of the molecular mechanism underlying the pathogenesis of thymoma with or without MG. Methods: Molecular profiles of thymoma with or without MG were downloaded from The Cancer Genome Atlas, and Pearson’s correlation analysis was performed to identify immune-related lncRNAs. T test was used to examine the differential expression and differential methylation between thymoma patients with or without MG. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to predict the function of target genes of immune-related lncRNAs. Results: Analyses of the 87 thymoma samples with complete MG information revealed that 205 mRNAs and 56 lncRNAs showed up-regulated expression in thymoma with MG patients, while 458 mRNAs and 84 lncRNAs showed down-regulated expression. The methylation level of three immune-related lncRNAs (AP000787.1, AC004943.1, WT1-AS, FOXG1-AS1) was significantly decreased in thymoma tissues, and the methylation level of these immune-related lncRNAs (WT1-AS: Cor = 0.368, p < 0.001; FOXG1-AS1: Cor = 0.288, p < 0.01; AC004943.1: Cor = -0.236, p < 0.05) correlated with their expression. GO and KEGG pathway analysis revealed that targets of the immune-related lncRNA FOXG1-AS1 were enriched in small GTPase binding and herpes simplex virus 1 infection. Transcription coregulator activity and cell cycle were the most enriched pathways for targets of lncRNA AC004943.1. LncRNA WT1-AS targets were most enriched in actin binding and axon guidance. Conclusion: Our results revealed the immune-related molecular profiling of thymoma with MG and without MG and identified key pathways involved in the underlying molecular mechanism of thymoma-related MG. These findings provide insights for further research of potential markers for thymoma-related MG.
Highlights
Thymoma is the most common anterior mediastinal tumor in adults, and approximately 50% of thymoma patients show myasthenia gravis (MG) (Garibaldi et al, 2020)
We further discovered that the methylation levels of immune-related Long noncoding RNAs (lncRNAs) AC004943.1, FOXG1-AS1 and WT1-AS regulated the expression of these lncRNAs, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed the functional pathways of the target genes of these immune-related lncRNAs
We found that DNA methylation in the promoter region of the lncRNA WT1-AS was significantly decreased in thymoma-related MG tissues compared with thymoma without MG and resulted in modulation of lncRNA expression levels, which may influence the expression of downstream genes that are related to the development of thymoma-related MG
Summary
Thymoma is the most common anterior mediastinal tumor in adults, and approximately 50% of thymoma patients show myasthenia gravis (MG) (Garibaldi et al, 2020). Thymectomy is effective for thymoma-associated MG, but the symptoms of some patients remain the same or become worse after surgical treatment (Kato et al, 2020). Thymoma-related MG is associated with abnormalities of the thymus, an important lymphoid organ that is closely related to immunity. Thymoma-related MG is usually more severe compared with generalized disease and is associated with bulbar and respiratory symptoms (Evoli et al, 2002). 50% of thymoma patients show myasthenia gravis (MG), which is an autoimmune disease; the pathogenesis of MG-associated thymoma remains elusive.
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