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Development and blind clinical validation of a microRNA based predictor of response to treatment with R-CHOEP in DLBCL

ABSTRACT: microRNAs er are group of short noncoding RNAs that regulate gene expression at the posttranslational level. It has been shown that mirs are independent predictios of outcome in patients with diffuse large b cell lymphoma treated with r-chop. Outcome in patients with dlbcl lymphoma treated with r-chop. Based on the measured GI50 in 60 human cell lines. 116 DLBCL samples

ORGANISM(S): Homo sapiens

SUBMITTER: Thomas Jensen

PROVIDER: E-GEOD-40239 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Development and blind clinical validation of a microRNA based predictor of response to treatment with R-CHO(E)P in DLBCL.

Knudsen Steen S Hother Christoffer C Grønbæk Kirsten K Jensen Thomas T Hansen Anker A Mazin Wiktor W Dahlgaard Jesper J Møller Michael Boe MB Ralfkiær Elizabeth E Brown Peter de Nully Pde N

PloS one 20150218 2

MicroRNAs (miRNA) are a group of short noncoding RNAs that regulate gene expression at the posttranscriptional level. It has been shown that microRNAs are independent predictors of outcome in patients with diffuse large B-cell lymphoma (DLBCL) treated with the drug combination R-CHOP. Based on the measured growth inhibition of 60 human cancer cell lines (NCI60) in the presence of doxorubicine, cyclophosphamide, vincristine and etoposide as well as the baseline microRNA expression of the 60 cell ...[more]

PMID: 25692889

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Development and blind clinical validation of a microRNA based predictor of response to treatment with R-CHOEP in DLBCL

Project description:microRNAs er are group of short noncoding RNAs that regulate gene expression at the posttranslational level. It has been shown that mirs are independent predictios of outcome in patients with diffuse large b cell lymphoma treated with r-chop. Outcome in patients with dlbcl lymphoma treated with r-chop. Based on the measured GI50 in 60 human cell lines.

2015-02-20 | GSE40239 | GEO

A multiomics approach in refractory DLBCL

Project description:Diffuse large B-cell lymphoma (DLBCL) is the most frequent entity among non-Hodgkin lymphoma (NHL). It is a clinically and biologically heterogeneous disease regarding treatment response and long-term outcome. The anthracycline-based regimen R-CHOP is still considered as the standard of care for first-line treatment allowing achieving a complete response for approximately 60% of the patients. The prognosis of patients with primary refractory or relapsed (R/R) disease is particularly poor with a median overall survival below one year. Only a fraction of R/R patients can be cured with salvage therapies due to the acquisition of chemoresistance. We conducted a large-scale and deep proteomic investigation of the proteome profiles of R/R DLBCL patients compared to chemosensitive patients in order to identify new potential biomarkers related to resistance to treatment and to better understand the biological mechanisms underlying chemoresistance.

2019-03-04 | PXD009089 | Pride

DFBL-18689-V2 PDX (ABC-DLBCL) tumors treated with miR-28 or control mimics

Project description:Diffuse large B cell lymphoma (DLBCL) is the most common aggressive B cell lymphoma and accounts for nearly 40% of cases of B cell non-Hodgkin lymphoma. DLBCL is generally treated with R-CHOP chemotherapy, but many patients do not respond or relapse after treatment. Here, we analyzed the therapeutic potential of the tumor suppressor microRNA-28 (miR-28) for DLBCL, alone and in combination with the Bruton’s tyrosine kinase inhibitor ibrutinib. Combination therapy with miR-28 plus ibrutinib potentiated the anti-tumor effects of monotherapy with either agent by inducing a specific transcriptional cell-cycle arrest program that impairs DNA replication. The molecular actions of miR-28 and ibrutinib synergistically impair DNA replication by simultaneous inhibition of origin activation and fork progression. Moreover, we found that downregulation of the miR-28-plus-ibrutinib gene signature correlates with better survival of ABC-DLBCL patients. These results provide evidence for the effectiveness of a new miRNA-based ibrutinib combination therapy for DLBCL and unveil the miR-28-plus-ibrutinib gene signature as a new predictor of outcome in ABC-DLBCL patients.

2023-09-21 | GSE229786 | GEO

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Project description:Diffuse large B-cell lymphoma (DLBCL) represents the most common subtype of malignant lymphoma and is heterogeneous with respect to morphology, biology, and clinical presentation.However, a robust prognostic factor based on cell biology of DLBCL has not yet been determined.To find the biomarker which may associate with clinical outcome in patients with DLBCL, microarray analysis was performed to screen a novel biomarker.

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Project description:Diffuse large B-cell lymphoma (DLBCL) is the most common B-cell malignancy with varying prognosis after the gold standard rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Several prognostic models have been established by focusing primarily on characteristics of lymphoma cells themselves, including cell-of-origin, genomic alterations, and gene/protein expressions. However, the prognostic impact of the lymphoma microenvironment and its association with characteristics of lymphoma cells are not fully understood. Using highly-sensitive transcriptome profiling of untreated DLBCL tissues, we here assess the clinical impact of lymphoma microenvironment on the clinical outcomes and pathophysiological, molecular signatures in DLBCL. The presence of normal germinal center (GC)-microenvironmental cells, including follicular T cells, macrophage/dendritic cells, and stromal cells, in lymphoma tissue indicates a positive therapeutic response. Our prognostic model, based on quantitation of transcripts from distinct GC-microenvironmental cell markers, clearly identified patients with graded prognosis independently of existing prognostic models. We observed increased incidences of genomic alterations and aberrant gene expression associated with poor prognosis in DLBCL tissues lacking GC-microenvironmental cells relative to those containing these cells. These data suggest that the loss of GC-associated microenvironmental signature dictates clinical outcomes of DLBCL patients reflecting the accumulation of “unfavorable” molecular signatures.

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Gene expression profiling of newly-diagnosed DLBCL samples with the NanoString nCounter technology

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DLBCL Patients

Project description:Genomic profiles of DLBCL (Diffuse Large B-cell Lymphoma) patients 20 DLBCL patients were selected for detection of genomic aberrations

2009-12-16 | GSE19459 | GEO

Gene expression of 61 FFPE tissues of DLBCL patients at high-risk (aaIPI 2 or 3)

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2023-08-16 | GSE156309 | GEO

caArray_golub-00095: Diffuse large B-cell lymphoma outcome prediction

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

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