Duodenal follicular lymphoma: comprehensive gene expression analysis with insights into pathogenesis.
Bottom Line: In contrast, protocadherin gamma subfamily genes were upregulated in DFL and NFL.Double immunofluorescence studies revealed that CCL20 and CCR6 were co-expressed in both DFL and MALT.We hypothesize that increased expression of CCL20 and MAdCAM-1 and co-expression of CCL20 and CCR6 may play an important role in tumorigenesis.
Affiliation: Department of Pathology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.Show MeSH
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Mentions: In order to summarize the biological features related to the transcriptomic alterations in lymphomas, 1708 downregulated and 1855 upregulated genes were separately subjected to GSEA with GO terms (Suppl. Table S5). GO terms representing immunity, such as “response to chemical stimulus” (corrected P-value, 1.015E-02), and, in another case, adhesion, such as “biological adhesion” (corrected P-value, 3.215E-02), were extracted for downregulated genes. For upregulated genes, GO terms related to immunity were listed in the top five as well. In subordinate positions, intriguingly, a term for “biological adhesion,” that is, “cell–cell adhesion” (corrected P-value, 3.837E-04), was listed (Suppl. Table S6). In the DFL versus NDU group, the top five upregulated genes were as follows: complement receptor 2, chemokine ligand 4 (CCL4), cannabinoid receptor 2 (macrophage), T-cell activation RhoGTPase activationg protein and interleukin 21 (IL-21). The top five downregulated genes were as follows: glutathione peroxidase 3, CDKN2B (p15), phospholipase A2 receptor 1, plasminogen activator and diacylglycerol lipase. In the NFL versus RLH group, the top five upregulated genes were protocadherin gamma subfamily B4, B3, B2, A5 and A3, and the top five downregulated genes were as follows: glucagon receptor, interferon-induced protein 44, discoidin domain receptor tyrosine kinase 1, claudin 3 and interferon alpha-inducible protein 6. In the MALT versus NDU group, the top five upregulated genes were as follows: Rho GTPase activating protein 17, Rap guanine nucleotide exchange factor 1, olfactory receptor family 2, transmembrane protein 40, and cholinergic receptor, nicotinic alpha 1. The top five downregulated genes were as follows: NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 1, beta subcomplex 8, alpha subcomplex 12, alpha subcomplex 13 and succinate dehydrogenase complex. As described further below, protocadherin gamma subfamily genes (PCDHGB3, A5, B2, A3, B4, B1, A7, A9, A8, B6, B7, A12 and A2) are linked to “cell–cell adhesion.” In order to focus on genes of interest, we narrowed down the original 2918 DEG to a smaller set of DEG (i.e. the second DEG set). In this case, we selected 116 upregulated and 445 downregulated genes that were linked to GO terms in the “biological process” category (Fig.2a,b). We then examined whether these 116 upregulated and 445 downregulated genes retained a similar clustering pattern to that of the initial 2918 DEG; indeed, we obtained a dendrogram in which DFL and MALT were separated from NFL (Fig. S3).
Affiliation: Department of Pathology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.