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Published in: BMC Cancer 1/2021

Open Access 01-12-2021 | Diffuse Large B-Cell Lymphoma | Research article

Establishment of a typing model for diffuse large B-cell lymphoma based on B-cell receptor repertoire sequencing

Authors: Wenhua Jiang, Hailong Wang, Shiyong Zhou, Guoqing Zhu, Mingyou Gao, Kuo Zhao, Limeng Zhang, Xiaojing Xie, Ning Zhao, Caijuan Tian, Zhenzhen Zhang, Fang Yan, Yi Pan, Pengfei Liu

Published in: BMC Cancer | Issue 1/2021

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Abstract

Background

The purpose of this study was to construct a new typing model for diffuse large B-cell lymphoma (DLBCL) patients based on the B-cell receptor (BCR) and explore its potential molecular mechanism.

Methods

BCR repertoire sequencing and whole-exome sequencing were performed on formalin-fixed paraffin-embedded samples from 12 DLBCL patients. Subsequently, a typing model was built with cluster analysis, and prognostic indicators between the two groups were compared to verify the typing model. Then, mutation and bioinformatics analyses were conducted to investigate the potential biomarkers of prognostic differences between the two groups.

Results

Based on BCR sequencing data, we divided patients into two clusters (cluster 1 and cluster 2); this classification differed from the traditional typing method (GCB and non-GCB), in which cluster 1 included some non-GCB patients. The progression-free survival (PFS), overall survival (OS), metastasis and Shannon diversity index of IGH V-J and survival after chemotherapy were significantly different (P < 0.05) between the two clusters, but no statistical significance was found between the GCB and non-GCB groups. The mutation status of 248 genes was significantly different between cluster 1 and cluster 2. Among them, FTSJ3, MAGED2, and ODF3L2 were the specific mutated genes in all patients in cluster 2, and these genes could be considered critical to the different prognoses of the two clusters of DLBCL patients.

Conclusion

We constructed a new typing model of DLBCL based on BCR repertoire sequencing that can better predict the survival time after chemotherapy. FTSJ3, MAGED2, and ODF3L2 may represent key genes for the difference in prognosis between the two clusters.
Literature
1.
go back to reference Masir N, Akhter A, Roshan TM, Florence CS, Abdul-Rahman F, Tumian NR, Kean-Chang P, Elyamany G, Shabani-Rad MT, Mansoor A. Diffuse large B-cell lymphoma in southeast Asian cohort: expression patterns of B-cell receptor (BCR) repertoire and its linkage with molecular subtypes and response to R-CHOP therapy. J Clin Pathol. 2019;72(9):630–5. https://doi.org/10.1136/jclinpath-2019-205837.CrossRefPubMed Masir N, Akhter A, Roshan TM, Florence CS, Abdul-Rahman F, Tumian NR, Kean-Chang P, Elyamany G, Shabani-Rad MT, Mansoor A. Diffuse large B-cell lymphoma in southeast Asian cohort: expression patterns of B-cell receptor (BCR) repertoire and its linkage with molecular subtypes and response to R-CHOP therapy. J Clin Pathol. 2019;72(9):630–5. https://​doi.​org/​10.​1136/​jclinpath-2019-205837.CrossRefPubMed
2.
go back to reference Xu W, Liang JH. Advances in novel genotyping and molecular targeting therapy for diffuse large B cell lymphoma. J Clin Hematol. 2020;33(9):594–8. Xu W, Liang JH. Advances in novel genotyping and molecular targeting therapy for diffuse large B cell lymphoma. J Clin Hematol. 2020;33(9):594–8.
4.
go back to reference Wilson WH, Young RM, Schmitz R, Yang Y, Pittaluga S, Wright G, Lih CJ, Williams PM, Shaffer AL, Gerecitano J, de Vos S, Goy A, Kenkre VP, Barr PM, Blum KA, Shustov A, Advani R, Fowler NH, Vose JM, Elstrom RL, Habermann TM, Barrientos JC, McGreivy J, Fardis M, Chang BY, Clow F, Munneke B, Moussa D, Beaupre DM, Staudt LM. Targeting B cell receptor signaling with ibrutinib in diffuse large B cell lymphoma. Nat Med. 2015;21(8):922–6. https://doi.org/10.1038/nm.3884.CrossRefPubMed Wilson WH, Young RM, Schmitz R, Yang Y, Pittaluga S, Wright G, Lih CJ, Williams PM, Shaffer AL, Gerecitano J, de Vos S, Goy A, Kenkre VP, Barr PM, Blum KA, Shustov A, Advani R, Fowler NH, Vose JM, Elstrom RL, Habermann TM, Barrientos JC, McGreivy J, Fardis M, Chang BY, Clow F, Munneke B, Moussa D, Beaupre DM, Staudt LM. Targeting B cell receptor signaling with ibrutinib in diffuse large B cell lymphoma. Nat Med. 2015;21(8):922–6. https://​doi.​org/​10.​1038/​nm.​3884.CrossRefPubMed
9.
go back to reference Tanaka S, Baba Y. B Cell Receptor Signaling. In: Wang JY, editor. B Cells in Immunity and Tolerance. Advances in Experimental Medicine and Biology. Springer, Singapore, vol. 1254; 2020. p. 23–36.CrossRef Tanaka S, Baba Y. B Cell Receptor Signaling. In: Wang JY, editor. B Cells in Immunity and Tolerance. Advances in Experimental Medicine and Biology. Springer, Singapore, vol. 1254; 2020. p. 23–36.CrossRef
11.
go back to reference Zhang F, Gan R, Zhen Z, Hu X, Li X, Zhou F, et al. Adaptive immune responses to SARS-CoV-2 infection in severe versus mild individuals. Sig Transduct Target Ther. 2020;5(156):1–11. Zhang F, Gan R, Zhen Z, Hu X, Li X, Zhou F, et al. Adaptive immune responses to SARS-CoV-2 infection in severe versus mild individuals. Sig Transduct Target Ther. 2020;5(156):1–11.
12.
go back to reference Khan TA, Friedensohn S, de vries Gorter AR, Straszewski J, Ruscheweyh H, Reddy ST. Accurate and predictive antibody repertoire profiling by molecular amplification fingerprinting. Sci Adv. 2016;2(3):e1501371.CrossRef Khan TA, Friedensohn S, de vries Gorter AR, Straszewski J, Ruscheweyh H, Reddy ST. Accurate and predictive antibody repertoire profiling by molecular amplification fingerprinting. Sci Adv. 2016;2(3):e1501371.CrossRef
13.
go back to reference Li JT, Zhang QY. Targeted therapy and immunotherapy in diffuse large B-cell lymphoma. Medical Recapitulate. 2019;25(12):2372–6. Li JT, Zhang QY. Targeted therapy and immunotherapy in diffuse large B-cell lymphoma. Medical Recapitulate. 2019;25(12):2372–6.
19.
go back to reference Papageorgio C, Brachmann R, Zeng J, Culverhouse R, Zhang WH, Mcleod H. MAGED2: a novel p53-dissociator. Int J Oncol. 2007;31(5):1205–11.PubMed Papageorgio C, Brachmann R, Zeng J, Culverhouse R, Zhang WH, Mcleod H. MAGED2: a novel p53-dissociator. Int J Oncol. 2007;31(5):1205–11.PubMed
Metadata
Title
Establishment of a typing model for diffuse large B-cell lymphoma based on B-cell receptor repertoire sequencing
Authors
Wenhua Jiang
Hailong Wang
Shiyong Zhou
Guoqing Zhu
Mingyou Gao
Kuo Zhao
Limeng Zhang
Xiaojing Xie
Ning Zhao
Caijuan Tian
Zhenzhen Zhang
Fang Yan
Yi Pan
Pengfei Liu
Publication date
01-12-2021
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2021
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-021-08015-z

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