Integrated Genomic and Transcriptomic Analyses of Diffuse Large B-Cell Lymphoma With Multiple Abnormal Immunologic Markers.

Lingshuang Sheng,Di Fu,Rong Shen,Yujia Huo,Shuo Wang,Pengpeng Xu,Yiwen Cao,Weili Zhao,Li Wang,Shu Cheng

doi:10.3389/fonc.2022.790720

Lingshuang Sheng, Di Fu + Show 8 more

Open Access

https://doi.org/10.3389/fonc.2022.790720

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Abstract

BackgroundDiffuse large B-cell lymphoma (DLBCL) is a highly aggressive subtype of lymphoma and related to autoimmune diseases (AIDs). Primary B-cell receptor-mediated AIDs are associated with poor clinical outcome of DLBCL. To further determine the role of immunological alterations on disease progression, our study integrated genomic and transcriptomic analyses on DLBCL with multiple abnormal immunologic markers.MethodsThe clinical data of 1,792 patients with newly diagnosed DLBCL were collected, with DNA- and RNA-sequencing conducted for 164 and 127 patients, respectively. Frequent gene mutations and the involved dysregulated pathways, along with gene expression pattern and tumor microenvironment alternations, were analyzed and compared based on the immune status of the patients.ResultsDLBCL with multiple abnormal immunologic markers demonstrated a variety of characteristics including elevated serum lactic dehydrogenase level, inferior prognosis, and dysregulated cell cycle and immune response, as well as activated oxidative phosphorylation pathway and increased Th1/Th2 and Th17/Treg ratios, which were highly similar as those that occur in AIDs.ConclusionsWe piloted the description of the clinical and genetic features of DLBCL with multiple abnormal immunologic markers, illustrated possible mechanisms of disease progression, and provided a clinical rationale of mechanism-based targeted therapy in this subset of DLBCL.

Highlights

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL) worldwide and represents a group of heterogeneous diseases with variable clinical features, genetic characteristics, treatment response, and disease outcome [1]
With durable remission achieved in 50%– 60% of the patients upon immunochemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP), the prognosis of DLBCL patients is impacted by multiple factors, including cell-of-origin (COO), B-cell lymphoma-2 (BCL-2)/MYC double expression (DEL), and double hit lymphoma (DHL)
Immune response is defined as any immune system process that functions in calibrated responses of an organism to a potential internal or external threat according to the Gene Ontology (GO) database, which is activated in various autoimmune diseases (AIDs) [5,6,7] and results in enhanced chronic immune activities and increased disease severity

Summary

Introduction

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL) worldwide and represents a group of heterogeneous diseases with variable clinical features, genetic characteristics, treatment response, and disease outcome [1]. Nongerminal center B-cell-like (non-GCB), DEL, and DHL subtypes of DLBCL have worse clinical outcome [2]. Epidemiological studies indicated a 5%–20% increased risk in DLBCL among patients with autoimmune diseases (AIDs) [3, 4]. B-cell receptor (BCR)mediated AIDs, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Sjögren’s syndrome (SS), often result in disease progression due to uncontrolled proliferation and transformation of malignant B cells [4]. Diffuse large B-cell lymphoma (DLBCL) is a highly aggressive subtype of lymphoma and related to autoimmune diseases (AIDs). Primary B-cell receptor-mediated AIDs are associated with poor clinical outcome of DLBCL. To further determine the role of immunological alterations on disease progression, our study integrated genomic and transcriptomic analyses on DLBCL with multiple abnormal immunologic markers

Methods

Results

Conclusion