Immune-Related Molecular Profiling of Thymoma With Myasthenia Gravis

Jinman Zhuang; Maohao Guan; Maolin Liu; Yuhang Liu; Shuyan Yang; Zhijian Hu; Fancai Lai; Fei He

doi:10.3389/fgene.2021.756493

Immune-Related Molecular Profiling of Thymoma With Myasthenia Gravis

Front Genet. 2021 Oct 28:12:756493. doi: 10.3389/fgene.2021.756493. eCollection 2021.

Authors

Jinman Zhuang^{1

2

3}, Maohao Guan⁴, Maolin Liu^{1

2

3}, Yuhang Liu^{1

2

3}, Shuyan Yang^{1

2

3}, Zhijian Hu^{1

2

3}, Fancai Lai⁴, Fei He^{1

2

3}

Affiliations

¹ Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou, China.
² Fujian Provincial Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China.
³ Fujian Digital Tumor Data Research Center, Fuzhou, China.
⁴ Department of Thoracic Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.

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.

Keywords: bioinformatics; functional enrichment analysis; immune-related lncRNAs; mg; thymoma.