MicroRNA Biomarkers in Canine Diffuse Large B-Cell Lymphoma

2020 ◽  
pp. 030098582096790
Author(s):  
Nelly O. Elshafie ◽  
Naila C. do Nascimento ◽  
Nathanael I. Lichti ◽  
Andrea L. Kasinski ◽  
Michael O. Childress ◽  
...  
Keyword(s):  
Gene Expression ◽  
B Cell ◽  
Cell Cycle Progression ◽  
Cell Lymphoma ◽  
Quantitative Polymerase Chain Reaction ◽  
B Cell Lymphoma ◽  
Molecular Diagnostic ◽  
Diagnostic Tools ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Lymphoma is among the most common cancer in dogs. Diffuse large B-cell lymphoma (DLBCL) is the predominant type, accounting for up to half of all cases. Definitive diagnosis of DLBCL relies on cytologic evaluation with immunophenotyping, or histopathology and immunohistochemistry when needed. A rapid and specific molecular test aiding in the diagnosis could be beneficial. Noncoding microRNAs (miRNAs) are regulators of gene expression involved in a variety of cellular processes, including cell differentiation, cell cycle progression, and apoptosis. Not surprisingly, miRNA expression is aberrant in diseases such as cancers. Their high stability and abundance in tissues make them promising biomarkers for diagnosing and monitoring diseases. This study aimed to identify miRNA signatures of DLBCL to develop ancillary molecular diagnostic tools. miRNA was isolated from formalin-fixed, paraffin-embedded lymph node tissue from 22 DLBCL and 14 nonneoplastic controls. Relative gene expression of 8 tumor-regulating miRNAs was achieved by RT-qPCR (reverse transcriptase quantitative polymerase chain reaction). The results showed downregulation of the let-7 family of miRNAs and miR-155, whereas miR-34a was upregulated in DLBCL compared to the controls. We demonstrated that the combination of expression levels of miR-34a and let-7f or of let-7b and let-7f achieved 100% differentiation between DLBCL and controls. Furthermore, let-7f alone discriminated DLBCL from nonneoplastic tissue in 97% of cases. Our results represent one step forward in search of a rapid and accurate ancillary diagnostic test for DLBCL in dogs.

scholarly journals Gene expression profiling-based risk prediction and profiles of immune infiltration in diffuse large B-cell lymphoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Selin Merdan ◽  
Kritika Subramanian ◽  
Turgay Ayer ◽  
Johan Van Weyenbergh ◽  
Andres Chang ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
B Cell ◽  
Risk Prediction ◽  
Expression Profiling ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Gene Signatures ◽  
Large B Cell Lymphoma ◽  
Large B Cell

AbstractThe clinical risk stratification of diffuse large B-cell lymphoma (DLBCL) relies on the International Prognostic Index (IPI) for the identification of high-risk disease. Recent studies suggest that the immune microenvironment plays a role in treatment response prediction and survival in DLBCL. This study developed a risk prediction model and evaluated the model’s biological implications in association with the estimated profiles of immune infiltration. Gene-expression profiling of 718 patients with DLBCL was done, for which RNA sequencing data and clinical covariates were obtained from Reddy et al. (2017). Using unsupervised and supervised machine learning methods to identify survival-associated gene signatures, a multivariable model of survival was constructed. Tumor-infiltrating immune cell compositions were enumerated using CIBERSORT deconvolution analysis. A four gene-signature-based score was developed that separated patients into high- and low-risk groups. The combination of the gene-expression-based score with the IPI improved the discrimination on the validation and complete sets. The gene signatures were successfully validated with the deconvolution output. Correlating the deconvolution findings with the gene signatures and risk score, CD8+ T-cells and naïve CD4+ T-cells were associated with favorable prognosis. By analyzing the gene-expression data with a systematic approach, a risk prediction model that outperforms the existing risk assessment methods was developed and validated.

scholarly journals Circulating long non-coding RNAs HOTAIR, Linc-p21, GAS5 and XIST expression profiles in diffuse large B-cell lymphoma: association with R-CHOP responsiveness

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mahmoud A. Senousy ◽  
Aya M. El-Abd ◽  
Raafat R. Abdel-Malek ◽  
Sherine M. Rizk
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Expression Profiles ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Diagnostic Tools ◽  
Large B Cell Lymphoma ◽  
Non Coding Rnas ◽  
Large B Cell

AbstractThe reliable identification of diffuse large B-cell lymphoma (DLBCL)-specific targets owns huge implications for its diagnosis and treatment. Long non-coding RNAs (lncRNAs) are implicated in DLBCL pathogenesis; however, circulating DLBCL-related lncRNAs are barely investigated. We investigated plasma lncRNAs; HOTAIR, Linc-p21, GAS5 and XIST as biomarkers for DLBCL diagnosis and responsiveness to R-CHOP therapy. Eighty-four DLBCL patients and thirty-three healthy controls were included. Only plasma HOTAIR, XIST and GAS5 were differentially expressed in DLBCL patients compared to controls. Pretreatment plasma HOTAIR was higher, whereas GAS5 was lower in non-responders than responders to R-CHOP. Plasma GAS5 demonstrated superior diagnostic accuracy (AUC = 0.97) whereas a panel of HOTAIR + GAS5 superiorly discriminated responders from non-responders by ROC analysis. In multivariate analysis, HOTAIR was an independent predictor of non-response. Among patients, plasma HOTAIR, Linc-p21 and XIST were correlated. Plasma GAS5 negatively correlated with International Prognostic Index, whereas HOTAIR positively correlated with performance status, denoting their prognostic potential. We constructed the lncRNAs-related protein–protein interaction networks linked to drug response via bioinformatics analysis. In conclusion, we introduce plasma HOTAIR, GAS5 and XIST as potential non-invasive diagnostic tools for DLBCL, and pretreatment HOTAIR and GAS5 as candidates for evaluating therapy response, with HOTAIR as a predictor of R-CHOP failure. We provide novel surrogates for future predictive studies in personalized medicine.

scholarly journals Plastin-3 is a diagnostic and prognostic marker for pancreatic adenocarcinoma and distinguishes from diffuse large B-cell lymphoma

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Fei Xiong ◽  
Guan-Hua Wu ◽  
Bing Wang ◽  
Yong-Jun Chen
Keyword(s):  
Lymph Node ◽  
B Cell ◽  
Cell Lymphoma ◽  
Quantitative Polymerase Chain Reaction ◽  
B Cell Lymphoma ◽  
Actin Binding ◽  
Rank Test ◽  
Large B Cell Lymphoma ◽  
Tissue Specimens ◽  
Large B Cell

Abstract Background Altered Plastin-3 (PLS3; an actin-binding protein) expression was associated with human carcinogenesis, including pancreatic ductal adenocarcinoma (PDA). This study first assessed differentially expressed genes (DEGs) and then bioinformatically and experimentally confirmed PLS3 to be able to predict PDA prognosis and distinguish PDA from diffuse large B-cell lymphoma. Methods This study screened multiple online databases and revealed DEGs among PDA, normal pancreas, diffuse large B-cell lymphoma (DLBCL), and normal lymph node tissues and then focused on PLS3. These DEGs were analyzed for Gene Ontology (GO) terms, Kaplan–Meier curves, and the log-rank test to characterize their association with PDA prognosis. The receiver operating characteristic curve (ROC) was plotted, and Spearman’s tests were performed. Differential PLS3 expression in different tissue specimens (n = 30) was evaluated by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Results There were a great number of DEGs between PDA and lymph node, between PDA and DLBCL, and between PDA and normal pancreatic tissues. Five DEGs (NET1, KCNK1, MAL2, PLS1, and PLS3) were associated with poor overall survival of PDA patients, but only PLS3 was further verified by the R2 and ICGC datasets. The ROC analysis showed a high PLS3 AUC (area under the curve) value for PDA diagnosis, while PLS3 was able to distinguish PDA from DLBCL. The results of Spearman's analysis showed that PLS3 expression was associated with levels of KRT7, SPP1, and SPARC. Differential PLS3 expression in different tissue specimens was further validated by RT-qPCR. Conclusions Altered PLS3 expression was useful in diagnosis and prognosis of PDA as well as to distinguish PDA from DLBCL.

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.

scholarly journals An NCCN-IPI based immune-related gene prognostic model for diffuse large B-cell lymphoma

2021 ◽  
Author(s):  
Shidai Mu ◽  
Deyao Shi ◽  
Lisha Ai ◽  
Fengjuan Fan ◽  
Fei Peng ◽  
...  
Keyword(s):  
Gene Expression ◽  
B Cell ◽  
Prognostic Model ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Significance ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Risk Patients ◽  
Large B Cell

AbstractBackgroundAn enhanced International Prognostic Index (NCCN-IPI) was built to better discriminate diffuse large B-cell lymphoma (DLBCL) patients in the rituximab era. However, there is an urgent need to identify novel valuable biomarkers in the context of targeted therapies, such as immune checkpoint blockade (ICB) therapy.MethodsGene expression data and clinical information were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. 73 immune-related hub genes in DLBCL patients with different IPI levels were identified by weighted gene co-expression network analysis (WGCNA), and 4 genes were selected to construct an IPI-based immune-related prognostic model (IPI-IPM). Afterward, the genetic, somatic mutational and molecular profiles of IPI-IPM subgroups were analyzed, as well as the potential clinical response of ICB in different IPI-IPM subgroups.ResultsThe IPI-IPM was constructed base on the expression of LCN2, CD5L, NLRP11 and SERPINB2, where high-risk patients had shorter overall survival (OS) than low-risk patients, consistent with the results in the GEO cohorts. The comprehensive results showed that a high IPI-IPM risk score was correlated with immune-related signaling pathways, high KMT2D and CD79B mutation rates, high infiltration of CD8+ T cells and macrophages (M1, M2), as well as up-regulation of inhibitory immune checkpoints including PD-L1, LAG3 and BTLA, indicating more potential response to ICB therapy.ConclusionThe IPI-IPM has independent prognostic significance for DLBCL patients, which provides an immunological perspective to elucidate the mechanisms on tumor progression and drug resistance, also sheds a light on developing immunotherapy for DLBCL.

Sign in / Sign up

Export Citation Format

Share Document