Expression profiling reveals specific gene expression signatures in gastric MALT lymphomas

Abstract

The purpose of this study is to identify genes that are involved in the etiology of Helicobacter pylori induced gastric MALT lymphoma. We compared gene expression profiles of gastric MALT lymphoma with their corresponding gastric MALT (chronic gastritis with formation of follicles and aggregates). cDNA microarrays were used to compare these two tissue types from the same patient (n = 21). Quantitative PCR and immunohistochemical staining were performed to validate the microarray results. Three hundred and fifty eight out of 11,552 genes were differentially expressed between gastric MALT lymphomas and gastric MALT. Thirty eight genes are implicated in immune response, 66 in signal transduction and 36 in cell proliferation. Interestingly, chromosome 6 was the only chromosome which was significantly over-represented with 25 genes (EASE score p = 0.01254). Several surface markers of haematopoietic cells, such as CD1c, CD40, CD44, CD53, CD83, CD86 and members of the HLA-D family were up-regulated in lymphoma tissues, indicating antigen-dependent survival of lymphoma cells. We conclude that gastric MALT lymphoma shows a specific gene expression profile, which allows the differentiation from H. pylori induced lymphoid gastritis.

Pre-Treatment Mutational and Transcriptomic Landscape of Responding Metastatic Melanoma Patients to Anti-PD1 Immunotherapy

“…It has both soluble and membrane forms, and is emerging as an interesting immune-modulating molecule [ 47 , 48 , 49 ]. Prior studies have shown that CD83 is a downstream target of NFkB , and can be detected on solid and hematologic malignancies, and has been shown to influence the tumor microenvironment [ 50 , 51 , 52 , 53 , 54 , 55 ]. In patients with Hodgkin lymphoma, it can be secreted from tumor cells to influence expression of PD1 in surrounding T cells [ 26 ], and there are promising results using nivolumab in Hodgkin lymphoma patients [ 56 , 57 ].…”

A Gain-Of-Function Mutation in the Plcg2 Gene Protects Mice from Helicobacter felis-Induced Gastric MALT Lymphoma

“…Series of 4 μm longitudinal sections were cut and stained with hematoxylin-eosin. Immunohistochemical stainings were conducted as previously described [ 12 ]. Following primary antibodies were used: monoclonal rat anti-mouse CD45R 1:200 (B220, clone RA3-6B2) (BD Pharmingen); polyclonal rabbit anti-cytokeratin 1:500 (catalogue number: Z0622; Dako GmbH).…”

“…Several studies showed that different host gene polymorphisms in genes such as IL-1 , CTLA4 and GST T1 are associated with increased inflammatory responses and consecutively with higher incidence of MALT lymphomas [ 8 – 11 ]. Previously, our group found that phospholipase C gamma 2 (PLCG2) is overexpressed in MALT lymphoma tissue [ 12 ]. In normal B-cells, B-cell receptor (BCR) antigen-binding results in PLCγ2 phosphorylation by Syk (spleen tyrosine kinase) and Btk (Bruton´s tyrosine kinase).…”

Targeting the Immune Microenvironment in Lymphomas of B-Cell Origin: From Biology to Clinical Application

“…Early studies suggested that Helicobacter pylori -specific tumor infiltrating T cells support the growth of MALT lymphoma cells [192]. A gene expression profiling study comparing non-malignant MALT tissue with MALT lymphoma tissue revealed an overexpression of CD1c, CD40, CD83, CD86, CD122 and HLA-D in the latter, suggesting the involvement of APCs and possibly T cells in this disease [193]. Infiltrating T cells are mostly Tregs and T H 2 cells [194], which are presumably attracted by tumor-secreted CCL17 and CCL22 and offer support via CD40-CD40L interaction [195].…”