META-ANALYSIS DISPLAYED TRANSCRIPTOMIC SIGNATURE OF DIFFUSE LARGE B-CELL LYMPHOMA WITH SIGNIFICANT DIFFERENCES BETWEEN SUBTYPES

• Published in: Hematology, Transfusion and Cell Therapy Vol. 44; pp. S93 - S94
• Main Authors: Mesquita, FP, Ferreira, SS, Silva, EL, Ribeiro, JKC, Aquino, PEA, Silva, ECE, Brunetta, DM, Carlos, LMB, Souza, PFN, Montenegro, RC
• Format: Journal Article
• Language: English
• Published: Elsevier España, S.L.U 01.10.2022
• ISSN: 2531-1379
• DOI: 10.1016/j.htct.2022.09.156

Lymphomas are cancers that affect the hematological system originated in the lymphatic system with an abnormal proliferation of lymphoid cells. Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma in adults. This lymphoma is well characterized by the presence of B-lineage lymphoid cells with immature features with diffuse proliferation in the affected tissue. This disease usually follows an aggressive clinical course, placing patients in immediate need of chemotherapeutic treatment. DLBCL can be further classified into two molecular subtypes, center-germinative B-cell (GCB) and activated B-cell (ABC) type lymphomas. This classification indicates the different stages of maturation of the neoplastic cells, and the different pathological mechanisms associated with them. The present work aimed to compare transcriptome signature of the center-germinative B-cell (GCB) and activated B-cell (ABC). Microarray studies were selected based on predefined criteria and downloaded from the GEO database. Data acquisition, processing, meta-data construction, as well as the differentially expressed genes were performed using R studio packages. Also, significantly enriched gene sets were identified using Gene Set Enrichment Analysis (GSEA). Gene expression and survival analysis from TCGA database were performed using the UALCAN and GEPIA webservers. From a total of 7,854 differentially expressed genes, 465 significantly down-regulated genes and 403 up-regulated genes in GCB subtype when compared to ABC subtype. Among these DEGs, in the GCB versus ABC comparison, the genes with the highest expression level were SPIN3 (FC: 1.12E+20), ZNF791 (FC: 9.43E+19) and TSPAN3 (FC: 9.18E+19), while the significant DEGs with the lowest expression level were KMT2C (FC: -3.09E+20), RIOX2 (FC: -1.49E+20) and ABHD11 (FC: -6.96E+19). Interestingly, only two genes had their expression levels significantly correlated to the DLBCL patient survival, the ABHD11 gene (p-value = 0.018) and MORF4L2 (p-value = 0.029). ABHD11 gene at low-medium level and MORF4L2 gene at high expression level significantly decrease the survival of patients. the meta-data generated from this study suggests that patients with diffuse large B-cell lymphoma pattern molecularly relevant gene expression in aspects related to cell proliferation, cell metabolism, and insensitivity to inhibitory signals to tumor progression as presented by the type of activated B cells. The findings converge the significant modulation of germinal center cells to gene expression regulation processes. Further experiments are still required, the transcriptional and translational activity, as well as cellular activity, appear to be decreased in the GCB type. Our findings, such as the one regarding the ABHD11 gene, which at low levels in GCB type, confers decreased survival rate in lymphoma patients. Therefore, this work brings important information for the understanding of the pathological process of the disease and its subtypes, and such biomarkers may serve as potential candidates for the development of molecular diagnostic methods and new therapeutic strategies for DLBCL subgroups.