Circulating miRNAs as biomarkers in diffuse large B-cell lymphoma: a systematic review

Abstract

Diffuse large B-cell lymphoma (DLBCL) is an aggressive and heterogeneous malignancy, with highly variable outcomes among patients. Although classification and prognostic tools have been developed, standard therapy still fails in 30-40% of patients. Hence, identification of novel biomarkers is needed. Recently, circulating microRNAs (miRNAs) have been suggested as non-invasive biomarkers in cancer. Our aim was to review the potential role of circulating miRNAs as biomarkers for diagnosis, classification, prognosis, and treatment response in DLBCL.We performed a search in PubMed using the terms [((‘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 identify articles that evaluated the impact of circulating miRNAs as diagnosis, subtype, treatment response or prognosis biomarkers in DLBCL in human population.Among the twelve articles that met the inclusion criteria, eleven considered circulating miRNAs as biomarkers for diagnosis, two for classification, and five for prognosis or treatment response. The limited number of studies performed and lack of consistency in results make it difficult to draw conclusions about the role of circulating miRNAs as non-invasive biomarkers in DLBCL. Although the preliminary associations observed seem promising, the only consistent result is the upregulation of mir-21 in DLBCL patients, which could be a biomarker for diagnosis. Further studies are needed.

MiRNA Dysregulation in Childhood Hematological Cancer

“…In lymphoma, Lawrie et al [ 207 ] showed miR-155, miR-210, and miR-21 in high levels in serum from DLBCL patients compared with healthy controls’ sera. Moreover, high miR-21 expression was associated with RFS [ 207 ], which was later confirmed by Chen et al [ 220 ] in an independent cohort; thus far, it is the only circulating miRNA in DLBC that has shown consistent results and is now considered a biomarker for diagnosis [ 221 ].…”

Circulating cell-free miR-494 and miR-21 are disease response biomarkers associated with interim-positron emission tomography response in patients with diffuse large B-cell lymphoma

“…MiR-494 was chosen for further evaluation as the archetypal exemplar of moMDSC-related miRNA. Despite not showing consistent DE, miR-21 and miR-155 were also included due to the findings in previous studies that showed they are enriched in DLBCL cell-lines and are elevated in the circulation at diagnosis [ 13 , 28 – 33 ].…”

“…It has been repeatedly recognized that c-f and PBMC miR-21 expression levels are elevated at diagnosis in DLBCL, with conflicting results regarding circulating miR-21's prognostic value [ 13 , 28 – 31 ]. To our knowledge, no studies of sequential c-f miR-21 once immuno-chemotherapy has been initiated and comparison with interim-PET/CT have been performed.…”

“…MiRNAs are ubiquitously dysregulated in a range of diseases and malignancies including DLBCL [ 9 – 11 ], and are enriched in a variety of cell types that are over-represented within the TME [ 12 ]. Not only are miRNA believed to both reflect and contribute to the underlying pathobiology of the aggressive B-cell lymphoma sub-type Diffuse Large B-cell Lymphoma (DLBCL), but they hold promise as both potential therapeutic targets and minimally-invasive circulating biomarkers [ 13 , 14 ].…”

MiR-28-5p mediates the anti-proliferative and pro-apoptotic effects of curcumin on human diffuse large B-cell lymphoma cells

“…Many miRNAs have been identified as biomarkers of B-cell lymphoma. 22 , 23 Schneider et al. 17 revealed that miR-28 expression is downregulated in B-cell lymphomas, suggesting that silencing of miR-28 will contribute to lymphomagenesis.…”