Exploring the cell-free total RNA transcriptome in diffuse large B-cell lymphoma and primary mediastinal B-cell lymphoma patients as biomarker source in blood plasma liquid biopsies

Frontiers in Oncology

Oncology

Dries Deeren¹  Katrien De Grove²  Fritz Offner²  Philippe Decruyenaere³  Jo Van Dorpe⁴  Malaïka Van der Linden⁴  Edoardo Giuili⁵  Jo Vandesompele⁶  Jasper Anckaert⁶  Kimberly Verniers⁶ 

[1] Department of Hematology, Algemeen Ziekenhuis (AZ) Delta Roeselare-Menen, Roeselare, Belgium;Department of Hematology, Ghent University Hospital, Ghent, Belgium;Department of Hematology, Ghent University Hospital, Ghent, Belgium;OncoRNALab, Cancer Research Institute Ghent (CRIG), Ghent University, Ghent, Belgium;Department of Biomolecular Medicine, Ghent University, Ghent, Belgium;Department of Pathology, Ghent University Hospital, Ghent, Belgium;Interuniversity Institute of Bioinformatics in Brussels (IB), Free University of Brussels, Brussels, Belgium;Department of Biotechnology and Pharmacy, University of Bologna, Bologna, Italy;OncoRNALab, Cancer Research Institute Ghent (CRIG), Ghent University, Ghent, Belgium;Department of Biomolecular Medicine, Ghent University, Ghent, Belgium;

关键词: cell-free RNA;    liquid biopsy;    blood plasma;    biomarkers;    DLBCL;    diffuse large B-cell lymphoma;    PMBCL;    primary mediastinal B-cell lymphoma;   

DOI  :  10.3389/fonc.2023.1221471

 received in 2023-05-12, accepted in 2023-09-18,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionDiffuse large B-cell lymphoma (DLBCL) and primary mediastinal B-cell lymphoma (PMBCL) are aggressive histological subtypes of non-Hodgkin’s lymphoma. Improved understanding of the underlying molecular pathogenesis has led to new classification and risk stratification tools, including the development of cell-free biomarkers through liquid biopsies. The goal of this study was to investigate cell-free RNA (cfRNA) biomarkers in DLBCL and PMBCL patients.Materials and methodsBlood plasma samples (n=168) and matched diagnostic formalin-fixed paraffin-embedded (FFPE) tissue samples (n=69) of DLBCL patients, PMBCL patients and healthy controls were collected between 2016-2021. Plasma samples were collected at diagnosis, at interim evaluation, after treatment, and in case of refractory or relapsed disease. RNA was extracted from 200 µl plasma using the miRNeasy serum/plasma kit and from FFPE tissue using the miRNeasy FFPE kit. RNA was subsequently sequenced on a NovaSeq 6000 instrument using the SMARTer Stranded Total RNA-seq pico v3 library preparation kit.ResultsHigher cfRNA concentrations were demonstrated in lymphoma patients compared to healthy controls. A large number of differentially abundant genes were identified between the cell-free transcriptomes of DLBCL patients, PMBCL patients, and healthy controls. Overlap analyses with matched FFPE samples showed that blood plasma has a unique transcriptomic profile that significantly differs from that of the tumor tissue. As a good concordance between tissue-derived gene expression and the immunohistochemistry Hans algorithm for cell-of-origin (COO) classification was demonstrated in the FFPE samples, but not in the plasma samples, a 64-gene cfRNA classifier was developed that can accurately determine COO in plasma. High plasma levels of a 9-gene signature (BECN1, PRKCB, COPA, TSC22D3, MAP2K3, UQCRHL, PTMAP4, EHD1, NAP1L1 pseudogene) and a 5-gene signature (FTH1P7, PTMAP4, ATF4, FTH1P8, ARMC7) were significantly associated with inferior progression-free and overall survival in DLBCL patients, respectively, independent of the NCCN-IPI score.ConclusionTotal RNA sequencing of blood plasma samples allows the analysis of the cell-free transcriptome in DLBCL and PMBCL patients and demonstrates its unexplored potential in identifying diagnostic, cell-of-origin, and prognostic cfRNA biomarkers.

【 授权许可】

Unknown   
Copyright © 2023 Decruyenaere, Giuili, Verniers, Anckaert, De Grove, Van der Linden, Deeren, Van Dorpe, Offner and Vandesompele

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