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

Abstract

Diffuse large B-cell lymphoma (DLBCL) is the most common histological subtype of non-Hodgkin’s lymphomas (NHL). DLBCL is an aggressive malignancy that displays a great heterogeneity in terms of morphology, genetics and biological behavior. While a sustained complete remission is obtained in the majority of patients with standard immunochemotherapy, patients with refractory of relapsed disease after first-line treatment have a poor prognosis. This patient group represents an important unmet need in lymphoma treatment. In recent years, improved understanding of the underlying molecular pathogenesis had led to new classification and prognostication tools, including the development of cell-free biomarkers in liquid biopsies. Although the majority of studies have focused on the use of cell-free fragments of DNA (cfDNA), there has been an increased interest in circulating-free coding and non-coding RNA, including messenger RNA (mRNA), microRNA (miRNA), long non-coding RNA (lncRNA) and circular RNA (circRNA), as well as RNA encapsulated in extracellular vesicles or tumor-educated platelets (TEPs). We performed a systematic search in PubMed to identify articles that evaluated circulating RNA as diagnostic, subtype, treatment response or prognostic biomarkers in a human DLBCL population. A total of 35 articles met the inclusion criteria. The aim of this systematic review is to present the current understanding of circulating RNA molecules as biomarker in DLBCL and to discuss their future potential.

Next-generation sequencing for MRD monitoring in B-lineage malignancies: from bench to bedside

“…Recently, liquid biopsy technology has emerged to capture information about SHM, V(D)J rearrangements, amplification and gene copy variations. By using circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), cell-free DNA (cfDNA), or other cell-free nucleic acids (mRNA, microRNA), liquid biopsy can be conducted in a noninvasive manner [ 126 ]. The results of several studies have suggested that ctDNA and cfDNA alone are practical for most lymphomas [ 5 ].…”

Screening for Prognostic microRNAs Associated with Treatment Failure in Diffuse Large B Cell Lymphoma

“…In this regard, our study avoided mixing of different DLBCL stages to guarantee congruent and clearly defined results. A more recent systematic review including more studies came to similar results and concluded that there is currently insufficient evidence, in particular, with respect to prediction of treatment response [ 26 ]. In this context, most studies analyze cell-free circulating miRNAs, and only very few reports are based on tissue samples [ 27 ].…”

Nucleic Acid Biomarkers in Waldenström Macroglobulinemia and IgM-MGUS: Current Insights and Clinical Relevance

“…In the past decade, there have been major advances in the identification of diagnostic, phenotype-defining and prognostic biomarkers in lymphoproliferative diseases, which might complement current classification and prognostic tools, as well as guide therapy choice in a precision medicine approach [183,184]. In blood-derived liquid biopsies, circulating cell-free tumor DNA (ctDNA) and RNA (ctRNA), circulating tumor cells (CTCs), and extracellular vesicles are released into the PB, reflecting the tumor-specific genetic profile of the primary tissue biopsy, as reported by independent studies in hematological malignancies [184][185][186].…”