MicroRNA Expression in High-Grade B-Cell Lymphoma With 11q Aberration

Abstract

Mature aggressive B-cell lymphomas, such as Burkitt lymphoma (BL) and Diffuse large B-cell lymphoma (DLBCL), show variations in microRNA (miRNA) expression. The entity of High-grade B-cell lymphoma with 11q aberration (HGBCL-11q) shares several biological features with both BL and DLBCL but data on its miRNA expression profile are yet scarce. Hence, this study aims to analyze the potential differences in miRNA expression of HGBCL-11q compared to BL and DLBCL. We evaluated the expression profiles of 2083 miRNAs in 25 HGCBL-11q, 7 BL, 131 DLBCL, and tonsils using the HTG EdgeSeq miRNA whole transcriptome assay. Uniform manifold approximation and projection (UMAP) and differential gene expression analyses based on DESeq2 were carried out. UMAP analysis of miRNA expression did not reveal distinct groups among the studied lymphomas. However, differential gene expression investigations detected sets of overexpressed miRNAs in HGBCL-11q when compared to BL (miR-9-3p, miR-9-5p, miR-3919, miR-129-1-3p, miR-129-2-3p, miR-331-3p, miR-196b-5p, and miR-28-5p) and DLBCL (miR-3919, miR-1290, miR-4538, and miR-4791), respectively. Notably, miR-3919 showed heterogeneous but significantly higher expression (p-value < 0.001) in HGBCL-11q than in both, BL and DLBCL. We identified a group of differentially expressed miRNAs between HGBCL-11q vs. BL and DLBCL, with miR-3919 as the most commonly and recurrently overexpressed miRNA in HGBCL-11q.

Keywords: Burkitt lymphoma; diffuse large B‐cell lymphoma; high‐grade B‐cell lymphoma with 11q aberration; micro‐RNAs.

FIGURE 1

MiRNA expression in HGBCL‐11q compared to BL and DLBCL. A: Overview of study cohort. Number of samples per group and miRNAs are indicated before and after QC with also the DE miRNAs. B: Uniform Manifold Approximation and Projection (UMAP, default parameters) based on the miRNA expression (n = 1978) of HGBCL‐11q (n = 25), BL (n = 7) and DLBCL (n = 131) and tonsillar controls (n = 11, two tonsils with 5 and 6 replicates). C: The volcano plot displays the DE miRNAs between HGBCL‐11q and BL using DESeq2. The DE miRNAs are colored according to their log2 fold change and adjusted p‐value, and the horizontal and vertical lines represent significance thresholds. Please note the different axis scaling in C and D. D: The volcano plot displays the DE miRNAs between HGBCL‐11q and DLBCL using DESeq2. The DE miRNAs are colored according to their log2 fold change and adjusted p‐value, and the horizontal and vertical lines represent significance thresholds. Please note the different axis scaling in C and D. E: Expression of miR‐3919 within the mature aggressive B‐cell lymphoma entities in this study: HGBCL‐11q (n = 25), BL (n = 7), DLBCL (n = 131) and tonsillar controls (n = 11, two tonsils with 5 and 6 replicates). Pairwise, two‐sided Wilcoxon test with Benjamini‐Hochberg correction for multiple testing. ***p < 0.001, ****p < 0.0001. Boxplot settings: Middle, median; lower hinge, 25% quantile; upper hinge, 75% quantile; upper/lower whisker, largest/smallest observation less/greater than or equal to upper/lower hinge ±1.5 * IQR. F: MiR‐3919 expression in HGBCL (HGBCL‐11q [n = 1], BL [n = 15], DLBCL [n = 11] and germinal center B cell populations [GCB cells, n = 3]) determined by small RNAseq within the ICGC MMML‐Seq project [7]. Boxplot settings: Middle, median; lower hinge, 25% quantile; upper hinge, 75% quantile; upper/lower whisker, largest/smallest observation less/greater than or equal to upper/lower hinge ±1.5 * IQR.