scholarly journals Gene expression profiles analysis identifies a novel two-gene signature to predict overall survival in diffuse large B-cell lymphoma

2019 ◽  
Vol 39 (1) ◽  
Author(s):  
Chengtao Sun ◽  
Xianfeng Cheng ◽  
Chaoyu Wang ◽  
Xi Wang ◽  
Bing Xia ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Overall Survival ◽  
Cell Lymphoma ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
B Cell Lymphoma ◽  
Ppi Network ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Diffuse large B-cell lymphoma (DLBCL) is the most common hematologic malignancy, however, specific tumor-associated genes and signaling pathways are yet to be deciphered. Differentially expressed genes (DEGs) were computed based on gene expression profiles from GSE32018, GSE56315, and The Cancer Genome Atlas (TCGA) DLBC. Overlapping DEGs were then evaluated for gene ontology (GO), pathways enrichment, DNA methylation, protein–protein interaction (PPI) network analysis as well as survival analysis. Seventy-four up-regulated and 79 down-regulated DEGs were identified. From PPI network analysis, majority of the DEGs were involved in cell cycle, oocyte meiosis, and epithelial-to-mesenchymal transition (EMT) pathways. Six hub genes including CDC20, MELK, PBK, prostaglandin D2 synthase (PTGDS), PCNA, and CDK1 were selected using the Molecular Complex Detection (MCODE). CDC20 and PTGDS were able to predict overall survival (OS) in TCGA DLBC and in an additional independent cohort GSE31312. Furthermore, CDC20 DNA methylation negatively regulated CDC20 expression and was able to predict OS in DLBCL. A two-gene panel consisting of CDC20 and PTGDS had a better prognostic value compared with CDC20 or PTGDS alone in the TCGA cohort (P=0.026 and 0.039). Overall, the present study identified a set of novel genes and pathways that may play a significant role in the initiation and progression of DLBCL. In addition, CDC20 and PTGDS will provide useful guidance for therapeutic applications.

Distinct Gene Expression Profiles: Nodal versus Extranodal Diffuse Large B-Cell Lymphoma

Oncology ◽  
2008 ◽  
Vol 75 (1-2) ◽  
pp. 71-80 ◽  
Author(s):  
Zeenath Jehan ◽  
Abdul K. Siraj ◽  
Jehad Abubaker ◽  
Christian Ruiz ◽  
Ronald Simon ◽  
...  
Keyword(s):  
Gene Expression ◽  
B Cell ◽  
Cell Lymphoma ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
B Cell Lymphoma ◽  
Distinct Gene ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Distinct types of primary cutaneous large B-cell lymphoma identified by gene expression profiling

Blood ◽  
2005 ◽  
Vol 105 (9) ◽  
pp. 3671-3678 ◽  
Author(s):  
Juliette J. Hoefnagel ◽  
Remco Dijkman ◽  
Katia Basso ◽  
Patty M. Jansen ◽  
Christian Hallermann ◽  
...  
Keyword(s):  
Gene Expression ◽  
B Cell ◽  
Cell Lymphoma ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
B Cell Lymphoma ◽  
European Organization ◽  
Large B Cell Lymphoma ◽  
First Choice ◽  
Large B Cell

AbstractIn the European Organization for Research and Treatment of Cancer (EORTC) classification 2 types of primary cutaneous large B-cell lymphoma (PCLBCL) are distinguished: primary cutaneous follicle center cell lymphomas (PCFCCL) and PCLBCL of the leg (PCLBCL-leg). Distinction between both groups is considered important because of differences in prognosis (5-year survival > 95% and 52%, respectively) and the first choice of treatment (radiotherapy or systemic chemotherapy, respectively), but is not generally accepted. To establish a molecular basis for this subdivision in the EORTC classification, we investigated the gene expression profiles of 21 PCLBCLs by oligonucleotide microarray analysis. Hierarchical clustering based on a B-cell signature (7450 genes) classified PCLBCL into 2 distinct subgroups consisting of, respectively, 8 PCFCCLs and 13 PCLBCLsleg. PCLBCLs-leg showed increased expression of genes associated with cell proliferation; the proto-oncogenes Pim-1, Pim-2, and c-Myc; and the transcription factors Mum1/IRF4 and Oct-2. In the group of PCFCCL high expression of SPINK2 was observed. Further analysis suggested that PCFCCLs and PCLBCLs-leg have expression profiles similar to that of germinal center B-cell–like and activated B-cell–like diffuse large B-cell lymphoma, respectively. The results of this study suggest that different pathogenetic mechanisms are involved in the development of PCFCCLs and PCLBCLs-leg and provide molecular support for the subdivision used in the EORTC classification.

scholarly journals Genome-wide DNA methylation and RNA-seq analyses identify genes and pathways associated with doxorubicin resistance in a canine diffuse large B-cell lymphoma cell line

PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0250013
Author(s):  
Chia-Hsin Hsu ◽  
Hirotaka Tomiyasu ◽  
Chi-Hsun Liao ◽  
Chen-Si Lin
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Rna Seq ◽  
Doxorubicin Resistance ◽  
Large B Cell Lymphoma ◽  
Genome Wide ◽  
Large B Cell

Doxorubicin resistance is a major challenge in the successful treatment of canine diffuse large B-cell lymphoma (cDLBCL). In the present study, MethylCap-seq and RNA-seq were performed to characterize the genome-wide DNA methylation and differential gene expression patterns respectively in CLBL-1 8.0, a doxorubicin-resistant cDLBCL cell line, and in CLBL-1 as control, to investigate the underlying mechanisms of doxorubicin resistance in cDLBCL. A total of 20289 hypermethylated differentially methylated regions (DMRs) were detected. Among these, 1339 hypermethylated DMRs were in promoter regions, of which 24 genes showed an inverse correlation between methylation and gene expression. These 24 genes were involved in cell migration, according to gene ontology (GO) analysis. Also, 12855 hypermethylated DMRs were in gene-body regions. Among these, 353 genes showed a positive correlation between methylation and gene expression. Functional analysis of these 353 genes highlighted that TGF-β and lysosome-mediated signal pathways are significantly associated with the drug resistance of CLBL-1. The tumorigenic role of TGF-β signaling pathway in CLBL-1 8.0 was further validated by treating the cells with a TGF-β inhibitor(s) to show the increased chemo-sensitivity and intracellular doxorubicin accumulation, as well as decreased p-glycoprotein expression. In summary, the present study performed an integrative analysis of DNA methylation and gene expression in CLBL-1 8.0 and CLBL-1. The candidate genes and pathways identified in this study hold potential promise for overcoming doxorubicin resistance in cDLBCL.

Characterizing Canine Lymphoma As a Potential Large Animal Model of Human Diffuse Large B-Cell Lymphoma

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5193-5193 ◽  
Author(s):  
Kristy L. Richards ◽  
Alison Motsinger-Reif ◽  
Hsiao-Wei Chen ◽  
Yuri D. Fedoriw ◽  
Cheng Fan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Animal Model ◽  
B Cell ◽  
Cell Lymphoma ◽  
Expression Profiles ◽  
B Cell Lymphoma ◽  
Large Animal Model ◽  
Large Animal ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Abstract 5193 Diffuse large B-cell lymphoma (DLBCL) affects ∼25,000 people in the U.S. each year, and fewer than half of them are cured with standard therapy. DLBCL can be divided into two subtypes by gene expression profiling, germinal center B-cell (GCB) type and activated B-cell (ABC) type. ABC-type DLBCL patients have significantly poorer outcomes. To improve therapeutic options, better animal models that accurately mimic human DLBCL (hDLBCL) are needed. Canine DLBCL is one of the most common cancers in veterinary oncology. Similar to human DLBCL patients, dogs with lymphoma are treated with both CHOP-like regimens and autologous stem cell transplants. Morphologically, canine lymphomas are similar to hDLBCL, with shared histologic markers, such as CD20 and PAX5. With recent technologies based on knowledge of the canine genome sequence, it is now possible to evaluate dogs as a potential large-animal model for hDLBCL. We evaluated 58 canine B-cell lymphomas by generating comprehensive gene expression profiles and comparing them to previously published hDLBCL expression profiles. Canine B-cell lymphoma expression profiles were similar in some ways to hDLBCLs. For instance, increased expression of NF-kB pathway genes was noted in a subset of lymphomas, mirroring NF-kB pathway activation in human ABC-type DLBCL. Furthermore, immunoglobulin heavy chain (IGH) mutation status, which is correlated with ABC/GCB cell of origin in hDLBCL, separated canine DLBCL into two groups with statistically different progression-free and overall survival times. However, canine DLBCL differed from hDLBCL in other aspects, including rare immunohistochemical positivity for BCL6 and MUM1/IRF4. Collectively, these results define aspects of canine B-cell lymphomas that resemble hDLBCL, identifying molecular similarities that could allow dogs to be used as a representative model of hDLBCL. Further comparative studies, including therapeutic trials, could potentially improve outcomes in both species. Disclosures: No relevant conflicts of interest to declare.

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