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

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.