Genes and pathways associated with the occurrence of malignancy in benign lymphoepithelial lesions

Abstract

There is increasing evidence concerning the occurrence of malignant lymphoma among people suffering from Mikulicz disease, also termed benign lymphoepithelial lesion (BLEL) and immunoglobulin G4-associated disease. However, the underlying molecular mechanism of the malignant transformation remains unclear. The present study aimed to investigate the gene expression profile between BLEL and malignant lymphoepithelial lesion (MLEL) conditions using tissue microarray analysis, to identify genes and pathways which may be associated with the risk of malignant transformation. Comparing gene expression profiles between BLEL tissues (n=13) and MLEL (n=14), a total of 1,002 differentially expressed genes (DEGs) were identified including 364 downregulated and 638 upregulated DEGs in BLEL. The downregulated DEGs in BLEL were frequently associated with immune-based functions, immune cell differentiation, proliferation and survival, and metabolic functions, whereas the upregulated DEGs were primarily associated with organ, gland and tissue developmental processes. The B cell receptor signaling pathway, the transcription factor p65 signaling pathway, low affinity immunoglobulin γ Fc region receptor II-mediated phagocytosis, the high affinity immunoglobulin ε receptor subunit γ signaling pathway and Epstein-Barr virus infection, and pathways in cancer, were the pathways associated with the downregulated DEGs. The upregulated DEGs were associated with three pathways, including glutathione metabolism, salivary secretion and mineral absorption pathways. These results suggested that the identified signaling pathways and their associated genes may be crucial for understanding the molecular mechanisms underlying malignant transformation from BLEL, and they may be considered to be markers for predicting malignancy among the BLEL group.

Clinical Features and Prognoses of IgG4-Positive and IgG4-Negative Lacrimal Lymphomas

“…Ohno ( 13 ) et al believe that IgG4+ marginal zone lymphoma is characterized by the up-regulation of Th2 and regulatory cytokines, and which is similar to IgG4-RD, but different from IgG4− marginal zone lymphoma, suggesting that the pathogenesis of IgG4+ lymphoma might be different from IgG4− lymphoma. Adzavon ( 14 ) et al preliminarily detected differentially expressed genes and pathways in IgG4-related dacryoadenitis and lymphoma using gene expression profile microarray analysis, which mainly focused on the B cell receptor signaling pathway, the NF-κB signaling pathway, FcγR mediated phagocytosis, the FcεRI signaling pathway, the EB virus infection signaling pathway, and the cancer signaling pathway.…”

The FcεRI signaling pathway is involved in the pathogenesis of lacrimal gland benign lymphoepithelial lesions as shown by transcriptomic analysis

“…LGBLEL is a chronic inflammatory disease, which clinical studies have indicated may be related to diseases including sinusitis and allergic rhinitis. Adzavon et al 24 found that the FcεRI signaling pathway may be involved in the mechanism that leads to malignant development in LGBLEL. The occurrence of malignant transformation is one of the pathological processes of LGBLEL; therefore, the FcεRI signaling pathway was examined in this study to further verify its role in LGBLEL pathogenesis.…”

The Involvement of the Fcεri Signaling Pathway in the Pathogenesis of Lacrimal Gland Benign Lymphoepithelial Lesions

“…LGBLEL is a chronic inflammatory disease, which clinical studies have indicated may be related to sinusitis, allergic rhinitis, and other diseases. Adzavon et al [16] found that the FcεRI signaling pathway may be involved in the mechanism leading to malignant development in LGBLEL. The occurrence of malignant transformation was one of the pathological processes of LGBLEL; therefore, the FcεRI signaling pathway was examined in this study to further verify its role in the LGBLEL pathogenesis.…”