Genes associated with the tumour microenvironment are differentially expressed in cured versus primary chemotherapy‐refractory diffuse large B‐cell lymphoma

Abstract

SummaryIn order to identify genes associated with primary chemotherapy‐resistance, gene expression profiles (GEP) in tumour tissue from 37 patients with de novo diffuse large B‐cell lymphoma (DLBCL), stage II–IV, either in continuous complete remission (n = 24) or with progressive disease during primary treatment (n = 13), were examined using spotted 55K oligonucleotide arrays. Immunohistochemistry was used for confirmation at the protein level. The top 86 genes that best discriminated between the two cohorts were chosen for further analysis. Only seven of 86 genes were overexpressed in the refractory cohort, e.g. RABGGTB and POLE, both potential targets for drug intervention. Seventy‐nine of 86 genes were overexpressed in the cured cohort and mainly coded for proteins expressed in the tumour microenvironment, many of them involved in proteolytic activity and remodelling of extra cellular matrix. Furthermore, major histocompatibility complex class I molecules, CD3D and ICAM1 were overexpressed, indicating an enhanced immunological reaction. Immunohistochemistry confirmed the GEP results. The frequency of tumour infiltrating lymphocytes, macrophages, and reactive cells expressing ICAM‐1, lysozyme, cathepsin D, urokinase plasminogen activator receptor, signal transducer and activator of transcription 1, and galectin‐3 was higher in the cured cohort. These findings indicate that a reactive microenvironment has an impact on the outcome of chemotherapy in DLBCL.

Experimental verification of a conserved intronic microRNA located in the human TrkC gene with a cell type-dependent apoptotic function

“…2c). MDN1 that is expressed in tumor microenvironment [32] is involved in RNA metabolism [33]. HBEGF is a known growth factor that is potentially involved in cell cycle [34].…”

The Gene Ontology Differs in Bursa of Fabricius Between Two Breeds of Ducks Post Hatching by Enriching the Differentially Expressed Genes

“…In the top 20 significantly DEGs, some of them are involved in apoptosis, such as TP53BP2 (Gorina & Pavletich, 1996) and ACTG2, and some of them take part in the regulation processes of gene expression, translation and protein modification, such as Med13l, DPP7, NELFA, Ctbp2, SERPINH1 (Christiansen, Schwarze & Pyott et al, 2010), PLEKHG4 and HTT. Some of the genes are related to the biological activities of B cells, such as CHRNB4, HFE (Drakesmith et al, 2002), PLEKHG4 and CD3D (Linderoth et al, 2008). These enriched DEGs are involved in different types of biological processes, which primarily supported the notion that multiple differences may exist in the BF between JCH and NH-P.…”

Favorable impact of the interleukin-4 receptor allelic variant I75 on the survival of diffuse large B-cell lymphoma patients demonstrated in a large prospective clinical trial

“…Recently, a higher expression of the IL4R in the germinal center B-cell-like DLBCL subgroup was shown and distinct functions of IL4 in the DLBCL subgroups were proposed [20,21]. Two publications based on gene expression profiling of DLBCL patients raised the possibility that an active immune response is favorable for DLBCL patients [22,23]. Thus, the favorable impact of the IL4R I75 variant on DLBCL outcome may be related to a more efficient immune response capacity against the lymphoma cells by enhanced IL4R expression or signal transduction capacities of the IL4R.…”