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Gene expression clusters change and molecular correlation via STING pathway between orbital MALT lymphoma and orbital IgG4-related eye diseases

ABSTRACT: Purpose: MALT lymphoma orbital region and IgG4-related eye disease (IGG4ROD) account for the majority of mass lesions in the orbital region. They may show similar shadows on radiological images, and many cases are difficult to differentiate clinically. We investigated what kind of gene expression cluster(RNA-seq) and molecular differences are responsible for two diseases. Methods: Total RNA was extracted from fresh tissues in 20 cases which were histopathologically diagnosed from 20XX to 20XX, and a sequence library was created. Next-generation sequencing analysis (RNA-seq, NovaSeq6000) was performed to compare gene expression between the two groups, and principal component analysis and cluster hierarchy analysis were performed. Results: In principal component analysis, orbital MALT lymphoma and IgG4ROD were clustered in component 2in PCA analysis. Clear cluster differences were observed, except for one case that appeared to be IgG4-producing MALT lymphoma. In addition, cluster analysis showed that one case that appeared to be IgG4-producing MALT lymphoma was located just between the IGG4ROD and MALT lymphoma clusters. Furthermore, in a comparison of up regulator analysis between IgG4ROD and MALT lymphoma, 582 genes were identified as candidates(p<0.01). Pathway analysis of MALT lymphoma suggested that the Sting pathway be activated. Sting pathway-down-stream analysis were significant eight gene expression changes)P<0.05). In addition, STING immunohistochmical analysis were detected different formed staining pattern using quantitative evaluation in IgG4ROD and MALT(P<0.01). Conclusion: MALT lymphoma orbital and IgG4-related eye disease (IGG4ROD) can be divided into two clusters of gene expression. The Sting pathway may be a important pathway specific to orbital MALT lymphoma compared with orbital IgG4ROD.

ORGANISM(S): Homo sapiens

PROVIDER: GSE276421 | GEO | 2025/09/01

REPOSITORIES: GEO

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Project description:Graves’ ophthalmopathy (GO) is an extrathyroidal complication of Graves’ hyperthyroidism. Orbital fibroblast, an important cell in the pathogenesis of GO, is responsible for GO characteristics during active and inactive stages; however, information on the extensive profiles and the mechanistic regulations behind orbital fibroblast phenotypes are currently limited. The aim of this study was to compare the proteome profile of orbital fibroblasts isolated from inactive GO, active GO and healthy control. The proteome profile was further integrated with global DNA methylation data to identify this epigenetics regulation involved in the pathogenesis of GO. Methods Orbital fibroblasts culture isolated from five inactive GO, four active GO and five controls were cultured for total protein and DNA extraction. The labelled and fractionated proteins were analyzed with a liquid chromatography tandem-mass spectrometer (LC-MS/MS). On the other hand, the bisulphite-treated DNA was measured with the Illumina Infinium Human Methylation 450K beadchip. Proteome and methylation data were validated by real-time quantitative (RQ)-PCR. Network, pathway and functional analysis were performed by Ingenuity (Qiagen). Results Orbital fibroblasts from active GO displayed overexpression of proteins typically involved with inflammation, cellular proliferation, hyaluronan synthesis and adipogenesis, while several proteins linked to extracellular matrix (ECM) biology and fibrotic disease were overexpressed in orbital fibroblasts from inactive GO. The DNA methylation patterns were similar in healthy control and inactive GO orbital fibroblasts which were distinct from active GO orbital fibroblasts. In orbital fibroblasts from active GO hypermethylated genes link to inflammation while those genes hypomethylated are involved in adipogenesis and autoimmune-related genes. For the network analysis, overlapped between hypermethylated and hypomethylated genes were observed including NF-B, ERK1/2, Alp, RNA polymerase II, Akt and IFNα. In addition, NF-κB, Akt and IFNα were also identified in networks from the differentially expressed proteins. In general, poor correlation between protein expression, DNA methylation and mRNA expression in our study was observed.

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Gene expression clusters change and molecular correlation via STING pathway between orbital MALT lymphoma and orbital IgG4-related eye diseases

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