Systematic Review of the Potential of MicroRNAs in Diffuse Large B Cell Lymphoma

Ane Larrabeiti-Etxebarria,Borja Santos-Zorrozua,Elixabet Lopez-Lopez,Africa Garcia-Orad,Maria Lopez-Santillan

doi:10.3390/cancers11020144

Abstract

Diffuse large B cell lymphoma (DLBCL) is the most common subtype of invasive non-Hodgkin’s lymphoma (NHL). DLBCL presents with variable backgrounds, which results in heterogeneous outcomes among patients. Although new tools have been developed for the classification and management of patients, 40% of them still have primary refractory disease or relapse. In addition, multiple factors regarding the pathogenesis of this disease remain unclear and identification of novel biomarkers is needed. In this context, recent investigations point to microRNAs as useful biomarkers in cancer. The aim of this systematic review was to provide new insight into the role of miRNAs in the diagnosis, classification, treatment response and prognosis of DLBCL patients. We used the following terms in PubMed” ((‘Non-coding RNA’) OR (‘microRNA’ OR ‘miRNA’ OR ‘miR’) OR (‘exosome’) OR (‘extracellular vesicle’) OR (‘secretome’)) AND (‘Diffuse large B cell lymphoma’ OR ‘DLBCL’)” to search for studies evaluating miRNAs as a diagnosis, subtype, treatment response or prognosis biomarkers in primary DLBCL in human patient populations. As a result, the analysis was restricted to the role of miRNAs in tumor tissue and we did not consider circulating miRNAs. A total of thirty-six studies met the inclusion criteria. Among them, twenty-one were classified in the diagnosis category, twenty in classification, five in treatment response and nineteen in prognosis. In this review, we have identified miR-155-5p and miR-21-5p as miRNAs of potential utility for diagnosis, while miR-155-5p and miR-221-3p could be useful for classification. Further studies are needed to exploit the potential of this field.

Highlights

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid malignancy in adults, accounting for 30–40% of all non-Hodgkin lymphoma cases [1]
The first line therapy for this aggressive malignancy consists of combined chemotherapy including rituximab, prednisone, doxorubicin, vincristine and cyclophosphamide (R-CHOP)
Another 63 articles were excluded because there were other coexisting pathologies, miRNAs were not analyzed in the tumor sample, DLBCL was not primarily considered, they did not assess the role of miRNAs in diagnosis, subtype, prediction of treatment response or prognosis, or miRNA expression changes were not considered

Summary

Introduction

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid malignancy in adults, accounting for 30–40% of all non-Hodgkin lymphoma cases [1]. DLBCL presents a very diverse clinical and genetic background, which leads to highly heterogeneous outcomes among patients [2]. The first line therapy for this aggressive malignancy consists of combined chemotherapy including rituximab, prednisone, doxorubicin, vincristine and cyclophosphamide (R-CHOP). Around 75–80% of patients achieve complete remission with R-CHOP therapy. Cancers 2019, 11, 144 patients have primary refractory disease or relapse [3]. Those patients tend to respond poorly to additional chemotherapy lines, which remains a major cause of morbidity and mortality [4]

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Conclusion