Gene expression signatures in multiple myeloma
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE125361 | GEO | 2020/01/24
REPOSITORIES: GEO
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Project description:Gene expression signatures in multiple myeloma
| PRJNA521958 | ENA
Project description:Multiple myeloma is a plasma cell malignancy of the bone marrow. Despite therapeutic advances, multiple myeloma remains incurable and better risk stratification as well as new therapies are therefore highly needed. The proteome of multiple myeloma has not been systematically assessed before and holds the potential to uncover additional insight into disease biology and improved prognostic models. Here, we provide a comprehensive multi-omics analysis including deep tandem mass tags (TMT)-based quantitative global (phospho)proteomics, RNA sequencing and nanopore DNA sequencing of 138 primary patient-derived plasma cell malignancies encompassing treatment-naive multiple myeloma patients treated in clinical trials, plasma cell leukemia, and the premalignancy monoclonal gammopathy of undetermined significance (MGUS), as well as healthy controls. We found that the (phospho)proteome of malignant plasma cells is highly deregulated as compared to healthy plasma cells and is both defined by chromosomal alterations and extensive post-transcriptional regulation. A protein signature was identified that is associated with aggressive disease and more predictive for outcome than cytogenetic-based risk assessment in newly diagnosed multiple myeloma. Integration with functional genetics and single-cell sequencing revealed generally and genetic subtype-specific deregulated proteins and pathways in plasma cell malignancies that include novel potential targets for (immuno)therapies. These findings provide new insights in the biology of multiple myeloma and will be a unique resource for investigating new therapeutic approaches.
2024-07-09 | PXD038437 | Pride
Project description:Multiple myeloma is a plasma cell malignancy of the bone marrow. Despite therapeutic advances, multiple myeloma remains incurable and better risk stratification as well as new therapies are therefore highly needed. The proteome of multiple myeloma has not been systematically assessed before and holds the potential to uncover additional insight into disease biology and improved prognostic models. Here, we provide a comprehensive multi-omics analysis including deep tandem mass tag (TMT)-based quantitative global (phospho)proteomics, RNA sequencing and nanopore DNA sequencing of 138 primary patient-derived plasma cell malignancies encompassing treatment-naive multiple myeloma patients treated in clinical trials, plasma cell leukemia, and the premalignancy monoclonal gammopathy of undetermined significance (MGUS), as well as healthy controls. We found that the (phospho)proteome of malignant plasma cells is highly deregulated as compared to healthy plasma cells and is both defined by chromosomal alterations and extensive post-transcriptional regulation. A protein signature was identified that is associated with aggressive disease and more predictive for outcome than cytogenetic-based risk assessment in newly diagnosed multiple myeloma. Integration with functional genetics and single-cell sequencing revealed generally and genetic subtype-specific deregulated proteins and pathways in plasma cell malignancies that include novel potential targets for (immuno)therapies. These findings provide new insights in the biology of multiple myeloma and will be a unique resource for investigating new therapeutic approaches.
2024-07-09 | PXD043580 | Pride
Project description:miRNA expression signatures in multiple myeloma
| PRJNA515993 | ENA
Project description:Multiple myeloma is a plasma cell malignancy of the bone marrow. Despite therapeutic advances in multiple myeloma, it remains incurable and better risk stratification as well as new therapies are therefore highly needed. While genetics and gene expression have been extensively studied leading to new insights in disease biology and improved prognostic models, the proteome of multiple myeloma has not been systematically assessed. Here, we provide a comprehensive multi-omic analysis including deep tandem mass tags (TMT)-based quantitative global (phospho)proteomics, RNA sequencing and nanopore DNA sequencing of 138 primary patient-derived plasma cell malignancy samples, including treatment-naive multiple myeloma cases selected for clinical trials, plasma cell leukemia, and the premalignancy MGUS, as well as healthy controls. We found that the (phospho)proteome of malignant plasma cells is highly deregulated as compared to healthy cells and is both defined by chromosomal alterations and extensive post-transcriptional regulation. A protein signature consisting of 8 proteins was identified that is associated with aggressive disease and highly predictive for outcomes in newly diagnosed multiple myeloma. Integration with functional genetics and single-cell sequencing revealed generally and genetic subtype-specific deregulated proteins and pathways in plasma cell malignancies that include novel potential targets for (immuno)therapies. Our study provides a unique resource for investigating biology and new therapeutic approaches in multiple myeloma and associated diseases and highlights the broad implications of proteomic studies in cancer.
2024-01-31 | GSE222727 | GEO
Project description:Multiple Myeloma (MM) is the second most prevalent blood cancer (10%) after non-Hodgkin's lymphoma and represents approximately 1% of all cancers and 2% of all cancer deaths. MM is a complex disease characterized by numerous genetic alterations and recent mRNA profiling studies have attempted to subclassify the disease to build pathogenetic and prognostic models Correct classification of cancer patients into subtypes is a prerequisite for acute diagnosis and effective treatment. Here we use high accuracy, quantitative proteomics to segregate cancer subtypes directly at the level of expressed proteins. Multiple myeloma is a heterogeneous disease in its initial clinical features as well as its outcome. We investigated two subtypes of Multiple Myeloma: multiple myeloma associated with t(4;14) chromosomal translocation as well as t(4;14)-negative MM subtype. The t(4;14) translocation, found in 15% of multiple myeloma cases, indicates a poor prognosis. Super-SILAC mix was combined of cell lysates from 8 diverse cell lines labelled with heavy amino acids (Lys8 and Arg10). The Super-SILAC library is mixed with samples (lysates), and quantitative mass spectrometric analysis is performed using a setup consisting of LC and on a linear ion trap Orbitrap mass spectrometer with high mass accuracy at the MS and MS/MS levels. This way we have analysed 20 patient samples from present MM. Shotgun proteomic analysis yielded a proteome of more than 5300 quantified proteins overall (3000 on an average per individual sample). High accuracy of quantification allowed robust separation of subtypes by hierarchical clustering on the protein level.
2024-07-15 | PXD003138 | Pride
Project description:The objective of this study is to identify genes involved in the pathogenesis of multiple myeloma (MM). In this study, we performed gene expression profiling of a total of 29 samples consisting of 19 clinical specimens, 7 myeloma cell lines and 3 normal samples. The microarray data were analysed by GeneSpring Software v14.9. A total of 5124 DEGs were identified in MM group vs control group (fold change≥2.0; P<0.05). Out of 5124 DEGs, 2696 and 2428 genes were up-regulated and down-regulated, respectively in MM group compared to the normal control group.
2022-07-20 | GSE72213 | GEO
Project description:In the present study, miRNome profiling was carried out to investigate the microRNA expression patterns of multiple myeloma patients and to assess the pathogenetic role of differentially expressed miRNAs by correlating their expression pattern with the expression of their target genes.
2020-01-24 | GSE125363 | GEO