Microrna expression distinguishes between germinal center B cell‐like and activated B cell‐like subtypes of diffuse large B cell lymphoma

Abstract

Diffuse large B cell lymphoma (DLBCL) is an aggressive malignancy that accounts for nearly 40% of all lymphoid tumors. This heterogeneous disease can be divided into germinal center B celllike (GCB) and activated B cell-like (ABC) subtypes by gene expression and immunohistochemical profiling. Using microarray analysis on prototypic cell lines, we identified microRNAs (miR-155, miR-21 and miR-221) that were more highly expressed in ABC-type than GCB-type cell lines. These microRNAs were over-expressed in de novo DLBCL (n 5 35), transformed DLBCL (n 5 14) and follicular center lymphoma cases (n 5 27) compared to normal B cells. Consistent with the cell line model, expression levels were higher in DLBCL cases with an ABC-type immunophenotype than those that were GCB-type (p < 0.05). Moreover, using multivariate analysis we found that expression of miR-21 was an independent prognostic indicator in de novo DLBCL (p < 0.05). Interestingly, expression levels of both miR-155 and miR-21 were also higher in nonmalignant ABC than in GCB cells. As we also demonstrate that expression of microRNAs can be measured reliably from routine paraffin-embedded biopsies of more than 8-years-old (p < 0.001), we suggest that microRNAs could be clinically useful molecular markers for DLBCL as well as other cancers. ' 2007 Wiley-Liss, Inc.

A 9 series microRNA signature differentiates between germinal centre and activated B-cell-like diffuse large B-cell lymphoma cell lines

“…By contrast to the findings of the present study, Lawrie et al (21) identified miR-21, miR-155 and miR-221 as discriminatory between ABC and GC with higher expression seen in ABC-type cell lines and also in patient material. miR-21 and miR-155 were confirmed to differentiate between ABC-and GC-like cell lines by another group (20).…”

“…This was most likely due to technical differences including sample preparation, array platforms and the control population used. Moreover, all three studies used a variety of cell lines with little or no overlap; one ABC and one GC type was common between the present investigation and Malumbres et al (20) and 2 GC types were used by both Lawrie et al and this study (21). Also, it is worth mentioning that the total number of microRNAs analysed in the present study was significantly higher than the previous two investigations (20,21) (420 vs 225 and 217, respectively) thus, including many more microRNAs which are differentially expressed between the DLBCL subgroups.…”

“…These authors were unable to distinguish GC-and ABC-like subgroups in 53 primary DLBCL tumours using the Malumbres 9 microRNA signature (44). By contrast, more recently, Lawrie et al using clinical samples have identified a discriminatory signature (23) that includes microRNAs which they previously reported as discriminatory (21), which correctly predicted lymphoma subtype and disease outcome (23).…”

“…Using cell lines of GC and ABC phenotypes, Malumbres et al identified a 9 microRNA signature that differentiated between these subgroups (20). Similarly, Lawrie et al reported that miR-21, -155 and -221 were significantly over-expressed in ABC-like cell lines compared to the GC type (21). More recently, two independent studies have reported predictive microRNA signatures for patients with DLBCL against those with FL (22,23) and also against normal lymph node B-cells (22).…”

Prognostic Role of microRNA-155 in Various Carcinomas: Results from a Meta-Analysis

“…After manually screening the titles, abstracts and key data, 259 records were excluded for not meeting the criteria listed above. Of the 28 reports selected for the systematic review, 12 studies were excluded in the final meta-analysis for lack of key HR value [21][22][23][24][25][26][27][28][29][30][31][32]. The excluded 12 studies commonly focused on other miRNAs and did not analyze the miR-155 data individually.…”