MicroRNA sequencing for biomarker detection in the diagnosis, classification and prognosis of Diffuse Large B Cell Lymphoma
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ABSTRACT:
PROVIDER: PRJNA770770 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR16304300.fastq.gz | Fastqsanger.gz | |||
| SRR16304301.fastq.gz | Fastqsanger.gz | |||
| SRR16304302.fastq.gz | Fastqsanger.gz | |||
| SRR16304303.fastq.gz | Fastqsanger.gz | |||
| SRR16304304.fastq.gz | Fastqsanger.gz |
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Project description:Diffuse Large B Cell Lymphoma (DLBCL) is the most common lymphoid malignancy in adults. Despite being considered a single disease, DLBCL presents with variable backgrounds in terms of morphology, genetics, and biological behavior, which results in heterogeneous outcomes among patients. Although new tools have been developed for the classification and management of patients, 40% of them still have primary refractory disease or relapse. In addition, multiple factors regarding the pathogenesis of this disease remain unclear and identification of novel biomarkers is needed. In this context, recent investigations point to microRNAs as useful biomarkers in cancer as well as important players in the development of the disease. However, regarding DLBCL, up to date, there is inconsistency in the data reported. Therefore, in this work, the main goals were to determine a microRNA set with utility as biomarkers for DLBCL diagnosis, classification, prognosis and treatment response. To achieve these goals, we analyzed microRNA expression in a cohort of 78 DLBCL samples at diagnosis and 17 controls using small RNA sequencing. This way, we were able to define new microRNA expression signatures for diagnosis, classification, treatment response and prognosis. In summary, our study remarks that microRNAs could play an important role as biomarkers in diagnosis, classification, treatment response and prognosis in DLBCL.
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Project description:Refractory/relapsed diffuse large B-cell lymphoma (DLBCL) has a poor prognosis. Novel drugs targeting the constitutively activated NF- B pathway characteristic of ABC-DLBCL are promising, but evaluation depends on accurate activated B cell-like (ABC)/germinal center B cell-like (GCB) molecular classification. This is traditionally performed on gene microarray expression profiles of fresh biopsies, which are not routinely collected, or by immunohistochemistry on formalin-fixed, paraffin-embedded (FFPE) tissue, which lacks reproducibility and classification accuracy. We explored the possibility of using routine archival FFPE tissue for gene microarray applications. We examined Affymetrix HG U133 Plus 2.0 gene expression profiles from paired archival FFPE and fresh-frozen tissues of 40 ABC/GCB-classified DLBCL cases to compare classification accuracy and test the potential for this approach to aid the discovery of therapeutic targets and disease classifiers in DLBCL. Unsupervised hierarchical clustering of unselected present probe sets distinguished ABC/GCB in FFPE with remarkable accuracy, and a Bayesian classifier correctly assigned 32 of 36 cases with >90% probability. Enrichment for NF- B genes was appropriately seen in ABC-DLBCL FFPE tissues. The top discriminatory genes expressed in FFPE separated cases with high statistical significance and contained novel biology with potential therapeutic insights, warranting further investigation. These results support a growing understanding that archival FFPE tissues can be used in microarray experiments aimed at molecular classification, prognostic biomarker discovery, and molecular exploration of rare diseases.
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Project description:This SuperSeries is composed of the SubSeries listed below: GSE56313 and GSE56314 Purpose Current diagnostic tests for diffuse large B-cell lymphoma use the updated WHO criteria based on biologic, morphologic, and clinical heterogeneity. We propose a refined classification sys-tem based on subset-specific B-cell–associated gene signatures (BAGS) in the normal B-cell hierarchy, hypothesizing that it can provide new biologic insight and diagnostic and prognostic value. Patients and Methods We combined fluorescence-activated cell sorting, gene expression profiling, and statistical modeling to generate BAGS for naive, centrocyte, centroblast, memory, and plasmablast B cells from normal human tonsils. The impact of BAGS-assigned subtyping was analyzed using five clinical cohorts (treated with cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP], n _ 270; treated with rituximab plus CHOP [R-CHOP], n _ 869) gathered across geo-graphic regions, time eras, and sampling methods. The analysis estimated subtype frequencies and drug-specific resistance and included a prognostic meta-analysis of patients treated with first-line R-CHOP therapy. Results Similar BAGS subtype frequencies were assigned across 1,139 samples from five different co-horts. Among R-CHOP–treated patients, BAGS assignment was significantly associated with overall survival and progression-free survival within the germinal center B-cell–like subclass; the centrocyte subtype had a superior prognosis compared with the centroblast subtype. In agreement with the observed therapeutic outcome, centrocyte subtypes were estimated as being less resistant than the centroblast subtype to doxorubicin and vincristine. The centroblast subtype had a complex genotype, whereas the centrocyte subtype had high TP53 mutation and insertion/deletion frequencies and expressed LMO2, CD58, and stromal-1–signature and major histocompatibility complex class II–signature genes, which are known to have a positive impact on prognosis. Conclusion Further development of a diagnostic platform using BAGS-assigned subtypes may allow pathogenetic studies to improve disease management.
2015-03-24 | GSE56315 | GEO
Project description:Purpose Current diagnostic tests for diffuse large B-cell lymphoma use the updated WHO criteria based on biologic, morphologic, and clinical heterogeneity. We propose a refined classification sys-tem based on subset-specific B-cell–associated gene signatures (BAGS) in the normal B-cell hierarchy, hypothesizing that it can provide new biologic insight and diagnostic and prognostic value. Patients and Methods We combined fluorescence-activated cell sorting, gene expression profiling, and statistical modeling to generate BAGS for naive, centrocyte, centroblast, memory, and plasmablast B cells from normal human tonsils. The impact of BAGS-assigned subtyping was analyzed using five clinical cohorts (treated with cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP], n _ 270; treated with rituximab plus CHOP [R-CHOP], n _ 869) gathered across geo-graphic regions, time eras, and sampling methods. The analysis estimated subtype frequencies and drug-specific resistance and included a prognostic meta-analysis of patients treated with first-line R-CHOP therapy. Results Similar BAGS subtype frequencies were assigned across 1,139 samples from five different co-horts. Among R-CHOP–treated patients, BAGS assignment was significantly associated with overall survival and progression-free survival within the germinal center B-cell–like subclass; the centrocyte subtype had a superior prognosis compared with the centroblast subtype. In agreement with the observed therapeutic outcome, centrocyte subtypes were estimated as being less resistant than the centroblast subtype to doxorubicin and vincristine. The centroblast subtype had a complex genotype, whereas the centrocyte subtype had high TP53 mutation and insertion/deletion frequencies and expressed LMO2, CD58, and stromal-1–signature and major histocompatibility complex class II–signature genes, which are known to have a positive impact on prognosis. Conclusion Further development of a diagnostic platform using BAGS-assigned subtypes may allow pathogenetic studies to improve disease management.
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Project description:Purpose Current diagnostic tests for diffuse large B-cell lymphoma use the updated WHO criteria based on biologic, morphologic, and clinical heterogeneity. We propose a refined classification sys-tem based on subset-specific B-cell–associated gene signatures (BAGS) in the normal B-cell hierarchy, hypothesizing that it can provide new biologic insight and diagnostic and prognostic value. Patients and Methods We combined fluorescence-activated cell sorting, gene expression profiling, and statistical modeling to generate BAGS for naive, centrocyte, centroblast, memory, and plasmablast B cells from normal human tonsils. The impact of BAGS-assigned subtyping was analyzed using five clinical cohorts (treated with cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP], n _ 270; treated with rituximab plus CHOP [R-CHOP], n _ 869) gathered across geo-graphic regions, time eras, and sampling methods. The analysis estimated subtype frequencies and drug-specific resistance and included a prognostic meta-analysis of patients treated with first-line R-CHOP therapy. Results Similar BAGS subtype frequencies were assigned across 1,139 samples from five different co-horts. Among R-CHOP–treated patients, BAGS assignment was significantly associated with overall survival and progression-free survival within the germinal center B-cell–like subclass; the centrocyte subtype had a superior prognosis compared with the centroblast subtype. In agreement with the observed therapeutic outcome, centrocyte subtypes were estimated as being less resistant than the centroblast subtype to doxorubicin and vincristine. The centroblast subtype had a complex genotype, whereas the centrocyte subtype had high TP53 mutation and insertion/deletion frequencies and expressed LMO2, CD58, and stromal-1–signature and major histocompatibility complex class II–signature genes, which are known to have a positive impact on prognosis. Conclusion Further development of a diagnostic platform using BAGS-assigned subtypes may allow pathogenetic studies to improve disease management.
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