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

// Maria Lopez-Santillan 1, 2, * , Ane Larrabeiti-Etxebarria 1, 3, * , Javier Arzuaga-Mendez 1, 4 , Elixabet Lopez-Lopez 1, ** and Africa Garcia-Orad 1, 5, ** 1 Department of Genetics, Physical Anthropology and Animal Physiology, Faculty of Medicine and Nursery, University of The Basque Country (UPV/EHU), Leioa, Spain 2 Medical Oncology Service, Basurto University Hospital, Bilbao, Spain 3 Pharmacy Service, Araba University Hospital-Txagorritxu, Vitoria, Spain 4 Hematology and Hemotherapy Service, Cruces University Hospital, Barakaldo, Spain 5 BioCruces Health Research Institute, Barakaldo, Spain * These authors share first authorship ** These authors share last authorship Correspondence to: Africa Garcia-Orad, email: africa.garciaorad@ehu.eus Keywords: lymphoma; circulating microRNA; diagnosis; classification; prognosis Received: February 23, 2018      Accepted: April 05, 2018      Published: April 27, 2018 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.