Abstract
BackgroundThe 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.MethodsBCR 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.ResultsBased 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.ConclusionWe 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.
Highlights
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
New typing model construction based on cluster analysis immunoglobulin heavy chain (IGH) complementarity determining region 3 (CDR3) contains 48 V and 6 J regions, which determine the specificity and partly reflect the diversity of BCR
In this study, we developed a novel typing model of DLBCL according to IGH V and J regions from the perspective of BCR repertoire sequencing and compared the predictive ability of DLBCL with traditional typing methods in prognosis and survival
Summary
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. Diffuse large B-cell lymphoma (DLBCL) is a moderately aggressive lymphoma originating from B cells and is the most common type of non-Hodgkin lymphoma (NHL). DLBCL is a heterogeneous disease due to its clinical manifestations and morphological and genetic characteristics [1]. Patients with DLBCL are divided into two subtypes according to gene expression profiling (GEP) technology, namely germinal centre B cell (GCB) type and activated B cell (ABC) type. A number of studies have found that DLBCL histological morphology, immunophenotype, genetic characteristics, and clinical incidence vary greatly among different cases. Accurate classification of DLBCL and clarification of its characteristics are important in the exploration of new therapeutic schemes
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