Dataset Information

Expression and polymorphisms of T cell immunoglobulin domain and mucin domain protein-1 in thymoma with or without myasthenia gravis.

ABSTRACT: The present study aimed to investigate the expression and association of the single-nucleotide polymorphism (SNP) -1637A/G in the promoter region of the T cell immunoglobulin domain and mucin domain protein-1 (Tim-1) gene in patients diagnosed with thymoma with or without myasthenia gravis (MG). The expression of Tim-1 was detected using the streptavidin peroxidase immunohistochemical staining method on tissues obtained from thymoma patients with (n=58) and without (n=62) MG. The Tim-1 gene -1637A/G polymorphism was detected using the single allele-specific primer polymerase chain reaction. The positive rate of Tim-1 expression in thymoma patients with MG was 62.1% (32/58), which was significantly higher compared with that in thymoma patients without MG (33.9%, 21/62) (P=0.002). The genotype frequencies of GG, GA and AA in the -1637A/G polymorphism were 0.7931, 0.2069 and 0, respectively, in thymoma patients with MG, and 0.6129, 0.3871 and 0, respectively, in thymoma patients without MG. A significant difference in the genotypes between the thymoma patients with MG and those without MG was found (P=0.031). In addition, a significant difference in allele frequencies between thymoma patients with MG and those without MG (P=0.024) was observed. The high expression of Tim-1 in thymoma tissues may play an important role in the development of thymoma with MG. The -1637A/G polymorphism site of the promoter region in Tim-1 may be associated with thymoma with MG. These findings provide a basis for further genetic research of thymoma with MG.

SUBMITTER: Zheng K

PROVIDER: S-EPMC4063586 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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Expression and polymorphisms of T cell immunoglobulin domain and mucin domain protein-1 in thymoma with or without myasthenia gravis.

Zheng Kai K Xu Guowu G Lu Xing X Zhang Jun J Zhang Peng P

Oncology letters 20140425 1

The present study aimed to investigate the expression and association of the single-nucleotide polymorphism (SNP) -1637A/G in the promoter region of the T cell immunoglobulin domain and mucin domain protein-1 (Tim-1) gene in patients diagnosed with thymoma with or without myasthenia gravis (MG). The expression of Tim-1 was detected using the streptavidin peroxidase immunohistochemical staining method on tissues obtained from thymoma patients with (n=58) and without (n=62) MG. The Tim-1 gene -163 ...[more]

PMID: 24959269

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Project description: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.

Project description:A unique feature of thymomas is their unrivaled frequency of associated myasthenia gravis (MG). Previous studies reported that MG+ thymomas contain a larger number of mature "pre-emigrant" CD4+ T cells than MG- thymomas and that most thymomas do not contain AIRE expressing cells irrespective of MG status. These findings suggest that CD4+ T cells that mature inside the abnormal microenvironment of thymomas and egress to the blood are critical to the development of thymoma-associated MG (TAMG) irrespective of thymoma histotype. However, underlying mechanisms have remained enigmatic. To get hints to mechanisms underlying TAMG, we pursue three hypotheses: (i) Functional pathways with metabolic and immunological relevance might be differentially expressed in TAMG(+) compared to TAMG(-) thymomas; (ii) differentially enriched pathways might be more evident in immature lymphocyte-poor (i.e., tumor cell/stroma-rich) thymoma subgroups; and (iii) mechanisms leading to TAMG might be different among thymoma histological subtypes. To test these hypotheses, we compared the expression of functional pathways with potential immunological relevance (N = 380) in relation to MG status separately in type AB and B2 thymomas and immature lymphocyte-rich and lymphocyte-poor subgroups of these thymoma types using the TCGA data set. We found that <10% of the investigated pathways were differentially upregulated or downregulated in MG+ compared to MG- thymomas with significant differences between AB and B2 thymomas. The differences were particularly evident, when epithelial cell/stroma-rich subsets of type AB and B2 thymomas were analyzed. Unexpectedly, some MG-associated pathways that were significantly upregulated in AB thymomas were significantly downregulated in B2 thymomas, as exemplified by the oxidative phosphorylation pathway. Conversely, the MG-associated pathway related to macrophage polarization was downregulated in MG+ AB thymoma and upregulated in MG+ B2 thymoma. We conclude that functional pathways are significantly associated with TAMG, and that some mechanisms leading to TAMG might be different among thymoma histological subtypes. Functions related to metabolisms, vascular and macrophage biology are promising new candidate mechanisms potentially involved in the pathogenesis of TAMG. More generally, the results imply that future studies addressing pathomechanisms of TAMG should take the histotype and abundance of tumor cells and non-neoplastic stromal components of thymomas into account.

Dataset Information

Expression and polymorphisms of T cell immunoglobulin domain and mucin domain protein-1 in thymoma with or without myasthenia gravis.

Publications

Expression and polymorphisms of T cell immunoglobulin domain and mucin domain protein-1 in thymoma with or without myasthenia gravis.

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