Immune-Related Molecular Profiling of Thymoma With Myasthenia Gravis

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.

Fatty acid metabolism-related lncRNAs are potential biomarkers for survival prediction in clear cell renal cell carcinoma

“…Furthermore, the signature has undergone verification in both the TCGA internal validation cohort and the E-MTAB-1980 validation cohort, thereby confirming its clinical practicability. The FAM-LPM was developed using fifteen prognostic FAM-associated lncRNAs, namely, CYTOR, LINC00894, [60] LINC01126, [61] AGAP2-AS1, [62] MIAT, [63] MIRLET7BHG, SNHG4, AATBC, WT1-AS, [64] SNHG17, C3orf35, TCL6, [65] MAPT-AS1, LINC00271, and BDNF-AS, some of these lncRNAs were identified as immune-related by Pearson's correlation test and are closely associated with cancer etiology and the prognosis of cancer patients. Compelling evidence has demonstrated a close connection between immunology and metabolism in cancer, as indicated by studies.…”

A new gene signature associated with disulfidptosis that forecasts myasthenia gravis and suggests infiltration of immune microenvironment in thymoma patients

“…For example, NEFM displays restricted sequence resemblance to primary autoimmune targets, while RYR3 demonstrates significant similarity [ 12 ]. Furthermore, prior research has shown that alterations in the expression of lncRNAs can play a crucial role in differentiating TAMG and uncovering the molecular mechanisms that contribute to its development [ 33 , 34 ]. Nevertheless, there has been no inquiry into the possible participation of DRLs.…”

Identification of m6A- and ferroptosis-related lncRNA signature for predicting immune efficacy in thymoma

“…As key regulators in the immune pathway 39,40 , lncRNAs are of key importance in directing the evolution of different immune cells and controlling dynamic transcriptional programs 41 . For example, lncRNA LOXL1-AS1 promotes HSPA9 expression, thereby promoting the growth and invasion of thymoma and thymic carcinoma cells and thus inhibiting apoptosis 42 ; XLOC_003810 is involved in the development and progression of thymoma combined with myasthenia gravis by regulating thymic helper T cell 17 (Th17)/regulatory T cell (Treg) balance 43 .In our study, we also found that patients with high risk scores had higher infiltration of immunosuppressive cells, such as macrophages M0/M1/M2 and dendritic cells, and lower infiltration of activated immune cells, such as type 2 helper T cells and T cells naive; and one regulatory immune cell that is critical for stimulation or suppression of immunity: the T follicular helper cell 44 (Figure 7A, B, 8E, K).…”