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.
DLBCL
PMBCL
biomarkers
blood plasma
cell-free RNA
diffuse large B-cell lymphoma
liquid biopsy
primary mediastinal B-cell lymphoma
Journal
Frontiers in oncology
ISSN: 2234-943X
Titre abrégé: Front Oncol
Pays: Switzerland
ID NLM: 101568867
Informations de publication
Date de publication:
2023
2023
Historique:
received:
12
05
2023
accepted:
18
09
2023
medline:
13
11
2023
pubmed:
13
11
2023
entrez:
13
11
2023
Statut:
epublish
Résumé
Diffuse 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. Blood 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. Higher 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 ( Total 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.
Identifiants
pubmed: 37954086
doi: 10.3389/fonc.2023.1221471
pmc: PMC10634215
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1221471Informations de copyright
Copyright © 2023 Decruyenaere, Giuili, Verniers, Anckaert, De Grove, Van der Linden, Deeren, Van Dorpe, Offner and Vandesompele.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Références
Mod Pathol. 2005 Oct;18(10):1377-84
pubmed: 15920548
STAR Protoc. 2021 Apr 14;2(2):100475
pubmed: 33937877
Blood Adv. 2022 Mar 22;6(6):1651-1660
pubmed: 35086141
Oncotarget. 2017 Mar 22;8(31):50949-50957
pubmed: 28881619
Oncotarget. 2018 Oct 5;9(78):34644-34657
pubmed: 30410665
Int J Oncol. 2005 Jan;26(1):151-7
pubmed: 15586235
Br J Haematol. 2021 Nov;195(3):399-404
pubmed: 34318932
BMC Cancer. 2022 Mar 29;22(1):339
pubmed: 35351053
Bioinformatics. 2015 Jan 15;31(2):166-9
pubmed: 25260700
Blood. 2017 Oct 19;130(16):1800-1808
pubmed: 28774879
J Transl Med. 2022 Jan 6;20(1):18
pubmed: 34991628
Biosci Rep. 2019 Aug 13;39(8):
pubmed: 31366566
Mol Oncol. 2020 Sep;14(9):1978-1997
pubmed: 32585766
Nature. 2000 Feb 3;403(6769):503-11
pubmed: 10676951
Blood. 2014 Feb 6;123(6):837-42
pubmed: 24264230
Nat Rev Cancer. 2011 Jun;11(6):426-37
pubmed: 21562580
Eur J Haematol. 2014;92(5):407-12
pubmed: 24400911
Blood. 2022 Mar 24;139(12):1863-1877
pubmed: 34932792
J Cancer. 2015 Aug 20;6(10):990-5
pubmed: 26366212
Aging (Albany NY). 2019 Oct 13;11(19):8068-8084
pubmed: 31631067
J Pathol Transl Med. 2022 Sep;56(5):281-288
pubmed: 36128864
Br J Haematol. 2013 Oct;163(1):123-6
pubmed: 23795711
Genome Biol. 2014;15(12):550
pubmed: 25516281
Int J Mol Sci. 2022 Oct 20;23(20):
pubmed: 36293478
Cancer Sci. 2014 Apr;105(4):437-44
pubmed: 24450488
Clin Cancer Res. 2021 Jan 15;27(2):513-521
pubmed: 33122345
J Clin Oncol. 2010 Apr 10;28(11):1896-903
pubmed: 20212248
Clin Proteomics. 2019 Apr 05;16:12
pubmed: 30988666
J Clin Oncol. 2018 Jul 10;36(20):2024-2034
pubmed: 29750632
J Clin Oncol. 2014 Sep 20;32(27):3059-68
pubmed: 25113753
Cancer. 2018 Dec 15;124(24):4622-4632
pubmed: 30252929
Blood Cancer Discov. 2022 Jan;3(1):50-65
pubmed: 35019856
Bioinformatics. 2019 Jul 1;35(13):2326-2328
pubmed: 30462173
Clin Exp Med. 2022 Feb;22(1):1-7
pubmed: 33990849
Sci Transl Med. 2016 Nov 9;8(364):364ra155
pubmed: 27831904
N Engl J Med. 2013 Apr 11;368(15):1408-16
pubmed: 23574119
J Clin Oncol. 2011 Jan 10;29(2):200-7
pubmed: 21135273
Front Oncol. 2020 Jul 21;10:1180
pubmed: 32850340
Gigascience. 2021 Feb 16;10(2):
pubmed: 33590861
Biology (Basel). 2019 Dec 22;9(1):
pubmed: 31877888
Cell Syst. 2015 Dec 23;1(6):417-425
pubmed: 26771021
Blood. 2022 Sep 1;140(9):955-970
pubmed: 34496020
J Mol Diagn. 2017 Nov;19(6):892-904
pubmed: 29054399
J Clin Oncol. 2015 Sep 10;33(26):2848-56
pubmed: 26240231
Blood. 2003 Dec 1;102(12):3871-9
pubmed: 12933571
Bioinformatics. 2016 Oct 1;32(19):3047-8
pubmed: 27312411
Blood Res. 2019 Jun;54(2):114-119
pubmed: 31309089
Nat Med. 2002 Jan;8(1):68-74
pubmed: 11786909
Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
pubmed: 16199517
Cell. 2017 Oct 5;171(2):481-494.e15
pubmed: 28985567
Cell Death Dis. 2015 Jan 29;6:e1621
pubmed: 25633290
Lancet. 2011 Nov 26;378(9806):1858-67
pubmed: 22118442
Blood. 2017 Apr 6;129(14):1947-1957
pubmed: 28096087
Blood. 2016 May 19;127(20):2375-90
pubmed: 26980727
Sci Rep. 2021 Jan 22;11(1):2095
pubmed: 33483590
Cell. 2015 Dec 3;163(6):1515-26
pubmed: 26627737
Int J Biochem Cell Biol. 2017 Apr;85:166-174
pubmed: 28259749
NPJ Precis Oncol. 2022 Apr 25;6(1):28
pubmed: 35468987
Mol Biol Rep. 2023 Feb;50(2):1133-1145
pubmed: 36409389
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
Bioinformatics. 2008 Mar 1;24(5):719-20
pubmed: 18024473
Cell. 2019 Jul 25;178(3):699-713.e19
pubmed: 31280963
Clin Med Res. 2010 Jul;8(2):84-8
pubmed: 20660931
PLoS One. 2009 Dec 15;4(12):e8173
pubmed: 20016842
Blood. 2017 Jun 8;129(23):3059-3070
pubmed: 28416502
Cells. 2020 Nov 28;9(12):
pubmed: 33260500
Transl Oncol. 2022 Feb;16:101314
pubmed: 34920339
Blood Cancer J. 2018 Aug 1;8(8):74
pubmed: 30069017
Lancet Oncol. 2015 May;16(5):541-9
pubmed: 25842160
Nucleic Acids Res. 2018 Nov 16;46(20):e119
pubmed: 30102402
Genome Res. 2017 Mar;27(3):491-499
pubmed: 28100584
EBioMedicine. 2022 Sep;83:104242
pubmed: 36054939
Blood. 2009 Apr 16;113(16):3773-80
pubmed: 19029441
Leuk Lymphoma. 2022 Apr;63(4):834-844
pubmed: 35075971
Semin Cancer Biol. 2019 Oct;58:100-108
pubmed: 30684535
Diagnostics (Basel). 2022 Jun 28;12(7):
pubmed: 35885481
Nucleic Acids Res. 2022 Jan 7;50(D1):D988-D995
pubmed: 34791404
Cancer Med. 2017 Apr;6(4):749-760
pubmed: 28332314
Oncotarget. 2017 Aug 7;8(42):72182-72196
pubmed: 29069778
Blood. 2004 Jan 1;103(1):275-82
pubmed: 14504078
Biomed Res. 2022;43(4):99-106
pubmed: 35989290
BMC Bioinformatics. 2011 Jan 26;12:35
pubmed: 21269502
J Exp Med. 2003 Sep 15;198(6):851-62
pubmed: 12975453
J Clin Oncol. 2018 Oct 1;36(28):2845-2853
pubmed: 30125215
Turk J Haematol. 2017 Aug 2;34(3):207-212
pubmed: 28148469
Exp Hematol Oncol. 2021 Feb 16;10(1):13
pubmed: 33593440
J Cancer. 2022 Feb 21;13(5):1388-1397
pubmed: 35371331
Leuk Lymphoma. 2017 May;58(5):1037-1051
pubmed: 27678023