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VDJ-Seq: Deep Sequencing Analysis of Rearranged Immunoglobulin Heavy Chain Gene to Reveal Clonal Evolution Patterns of B Cell Lymphoma
Published on: December 28, 2015
Identifying Distinct Molecular Subtypes and Establishing a Prognostic Framework for DLBCL Patients via Multiomics
Hongyu Shen1,2, Jinbo Lu3, Qi Yan4
1Department of Hematology, The First Affiliated Hospital With Nanjing Medical University, Jiangsu Province Hospital, Nanjing, Jiangsu, China, jsph.net.
None:
Diffuse large B-cell lymphoma (DLBCL) is characterized by profound heterogeneity that underpins varied clinical outcomes. To decipher this complexity, we performed an integrated single-cell and genomic analysis. Using scRNA-seq data (GSE182434), we identified six distinct malignant B-cell subclusters (MB1-MB6) within the DLBCL ecosystem. Cell-cell communication analysis revealed intricate interaction networks, particularly involving the MIF and Complement pathways. Prognostic analysis of bulk transcriptomic data (GSE32918) identified the MB5-related gene signature as the most critical factor associated with poor overall survival. This MB5 subgroup was associated with enhanced proliferative processes, a higher tumor mutational burden, and specific comutations. Leveraging MB5 marker genes, we developed and validated a robust CoxBoost-RSF machine-learning model that effectively stratified patient risk in independent cohorts. Our study defines the MB5 malignant B-cell subgroup as a key driver of DLBCL aggressiveness and provides both a novel prognostic biomarker and a framework for personalized therapeutic targeting.
