Prognostic microRNA profiling signatures in primary testicular diffuse large B-cell lymphoma
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PROVIDER: PRJNA1268782 | ENA |
REPOSITORIES: ENA
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Project description:Primary testicular (PT) diffuse large B-cell lymphoma (DLBCL) is a rare and aggressive lymphoma with distinct clinical and molecular characteristics. To further improve the prognosis of PT-DLBCL, not only the common features of PT-DLBCL, but also the molecular heterogeneity within the PT-DLBCL entity, need to be better understood. In this study, 2083 microRNAs and 13 housekeeping genes in RNA samples from 150 patients with PT-DLBCL were sequenced using next-generation sequencing technology. After quality-control, CPM standardization, and normalization, microRNA profiling data were obtained for 113 patients with PT-DLBCL. Our analysis identified a microRNA signature (comprising 35 microRNAs) that clustered 113 patients with PT-DLBCL into two distinct clusters. Patients with high expression of 16 microRNAs (miR-514a-3p, miR-202-3p, miR-509-5p, miR-509-3-5p, miR-506-3p, miR-508-3p, miR-514b-5p, miR-513a-5p, miR-510-5p, miR-513b-5p, miR-513c-5p, miR-508-5p, miR-509-3p, miR-202-5p, miR-507, and miR-514b-3p) had significantly better survival.
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Project description:The aggressive B cell lymphoma diffuse large B cell lymphoma (DLBCL) is a heterogeneous entity that requires more precise monitoring and prognosis molecular tools. Extracellular vesicles that are secreted by all cell types are currently recognized as serving as a proxy for the cell of origin. Utilizing cutting-edge mass spectrometry, the current study described and assessed the plasma small extracellular vesicles (sEVs) proteome's diagnostic and prognostic potential. The presence of DLBCL has a significant impact on the sEV proteome, and several proteins substantially correlate with DLBCL.Nevertheless, no proteins that highly correlated with non-GCB or GCB were found.
2023-03-11 | PXD036735 | Pride
Project description:Diffuse large B-cell lymphoma (DLBCL), the most common lymphoid malignancy in adults, is curable in less than 50% of patients. Prognostic models based on pre-treatment characteristics, such as the International Prognostic Index (IPI), are currently used to predict outcome in DLBCL. However, clinical outcome models identify neither the molecular basis of clinical heterogeneity, nor specific therapeutic targets. We analyzed the expression of 6,817 genes in diagnostic tumor specimens from DLBCL patients who received cyclophosphamide, adriamycin, vincristine and prednisone (CHOP)-based chemotherapy, and applied a supervised learning prediction method to identify cured versus fatal or refractory disease. The algorithm classified two categories of patients with very different five-year overall survival rates (70% versus 12%). The model also effectively delineated patients within specific IPI risk categories who were likely to be cured or to die of their disease. Genes implicated in DLBCL outcome included some that regulate responses to B-cell-receptor signaling, critical serine/threonine phosphorylation pathways and apoptosis. Our data indicate that supervised learning classification techniques can predict outcome in DLBCL and identify rational targets for intervention. golub-00095 Assay Type: Gene Expression Provider: Affymetrix Array Designs: Hu6800 Organism: Homo sapiens (ncbitax) Tissue Sites: Lymphoid tissue Material Types: synthetic_DNA, synthetic_RNA, organism_part Cell Types: B-Lymphocyte Disease States: Diffuse large B-cell Lymphoma, Follicular Lymphoma
2015-05-15 | E-GEOD-68895 | biostudies-arrayexpress
Project description:Elevated level of circulating cell-free DNA (cfDNA) has been associated with poor prognosis and relapse in patients with diffuse large B-cell lymphoma (DLBCL), but the tumor-specific molecular alterations in cfDNA with prognostic significance remain unclear. We investigated the association between 5-hydroxymethylcytosines (5hmC), a mark of active demethylation and gene activation, in cfDNA from blood plasma and prognosis in DLBCL. We used the 5hmC-Seal, a highly sensitive chemical labeling technique, to profile genome-wide 5hmC in plasma cfDNA samples from 48 newly diagnosed patients with DLBCL at the University of Chicago between 2010 and 2012. Patients were followed through December 31, 2017. We found a distinct genomic distribution of 5hmC in cfDNA marking tissue-specific enhancers, consistent with their potential roles in gene regulation. The 5hmC profiles in cfDNA differed by cell-of-origin, and were associated with clinical prognostic features including Ann Arbor stage, serum lactate dehydrogenase (LDH) level, and the International Prognostic Index (IPI). We developed a 29 gene-based weighted prognostic score (wp-score) for predicting event-free survival (EFS) and overall survival (OS), by applying the elastic net regularization on the Cox proportional hazard model. The wp-scores showed significantly improved prognostic accuracy and/or sensitivity/specificity than the established prognostic factors. In multivariate Cox models, patients with high wp-scores were associated with worse event-free survival (Hazard Ratio [HR] = 9.17, 95% confidence interval [CI] = 2.01- 41.89, p = 0.004), compared with those in the low risk group. Our findings suggest that the 5hmC signatures in cfDNA at the time of diagnosis are associated with clinical outcomes in DLBCL and may provide a novel non-invasive prognostic approach for DLBCL.
2019-11-15 | GSE126676 | GEO
Project description:Transformation of Follicular Lymphoma to Diffuse Large Cell Lymphoma: Alternative Patterns with Increased or Decreased Expression of c-myc and its Regulated genes The natural history of follicular lymphoma (FL) is frequently characterized by transformation to a more aggressive diffuse large B cell lymphoma (DLBCL). We compared the gene expression profiles between transformed DLBCL and their antecedent FL. No genes were observed to increase or decrease their expression in all the cases of histological transformation. However, two different gene expression profiles associated with the transformation process were defined, one in which c-myc and genes regulated by c-myc showed increased expression and one in which these same genes showed decreased expression. Further, there was a striking difference in gene expression profiles between transformed DLBCL and de novo DLBCL, since the gene expression profile of transformed DLBCL was more similar to their antecedent FL than to de novo DLBCL. The study demonstrates that transformation from FL to DLBCL can occur by alternative pathways and that transformed DLBCL and de novo DLBCL have very different gene expression profiles that may underlie the different clinical behaviors of these two types of morphologically similar lymphomas.
2005-09-23 | E-SMDB-963 | biostudies-arrayexpress
Project description:We performed DNA methylation (HELP) and gene expression profiling in 69 samples of diffuse large B cell lymphoma (DLBCL). First, by gene expression, two molecular subtypes of DLBCL termed as germinal center B cell-like (GCB) and activated B cell-like (ABC) DLBCL were assigned to the 69 DLBCL cases. Then, we performed supervised analysis using HELP data and defined DNA methylation signature differentiating 2 subgroups of DLBCLs. Keywords: DNA methylation profiling
2010-09-03 | GSE23967 | GEO
Project description:The survival of patients with diffuse large-B-cell lymphoma after chemotherapy is influenced by molecular features of the tumors. We used the gene-expression profiles of these lymphomas to develop a molecular predictor of survival. METHODS: Biopsy samples of diffuse large-B-cell lymphoma from 240 patients were examined for gene expression with the use of DNA microarrays and analyzed for genomic abnormalities. Subgroups with distinctive gene-expression profiles were defined on the basis of hierarchical clustering. A molecular predictor of risk was constructed with the use of genes with expression patterns that were associated with survival in a preliminary group of 160 patients and was then tested in a validation group of 80 patients. The accuracy of this predictor was compared with that of the international prognostic index. RESULTS: Three gene-expression subgroups--germinal-center B-cell-like, activated B-cell-like, and type 3 diffuse large-B-cell lymphoma--were identified. Two common oncogenic events in diffuse large-B-cell lymphoma, bcl-2 translocation and c-rel amplification, were detected only in the germinal-center B-cell-like subgroup. Patients in this subgroup had the highest five-year survival rate. To identify other molecular determinants of outcome, we searched for individual genes with expression patterns that correlated with survival in the preliminary group of patients. Most of these genes fell within four gene-expression signatures characteristic of germinal-center B cells, proliferating cells, reactive stromal and immune cells in the lymph node, or major-histocompatibility-complex class II complex. We used 17 genes to construct a predictor of overall survival after chemotherapy. This gene-based predictor and the international prognostic index were independent prognostic indicators.
2016-12-07 | GSE90953 | GEO
Project description:We performed DNA methylation (HELP) and gene expression profiling in 69 samples of diffuse large B cell lymphoma (DLBCL). First, by gene expression, two molecular subtypes of DLBCL termed as germinal center B cell-like (GCB) and activated B cell-like (ABC) DLBCL were assigned to the 69 DLBCL cases. Then, we performed supervised analysis using HELP data and defined DNA methylation signature differentiating 2 subgroups of DLBCLs. Keywords: DNA methylation profiling The retrospective study included DNA extracted from 69 clinical samples. [This Series represents the DNA methylation profiling component of the study.]
2010-09-03 | E-GEOD-23967 | biostudies-arrayexpress
Project description:Spatially-resolved transcriptomics reveal macrophage heterogeneity and prognostic significance in diffuse large B-cell lymphoma
| PRJNA974073 | ENA