Gene Expression profiling of Multiple Myeloma
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Nikhil Munshi
PROVIDER: E-GEOD-39754 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:We have analyzed gene expression microarray datasets from four different clinical trials to assess accuracy of gene expression based signature in predicting treatment complete response in patients with multiple myeloma. Two of four datasets were made available via The Intergroupe Francophone du Myélome (IFM) group, and remaining two datasets were downloaded from NCBI GEO portal with accession IDs: GSE19784 (HOVON65/GMMG-HD4 trial) and GSE9782 (APEX/SUMMIT trial). Analysis UUID: datasets_archive--2afcd42a-7e12-11e3-9145-5fcc1e060548--15-Jan-2014-12-23-44-CST. Following dataset provides gene expression microarray dataset for IFM-2005 trial involving 67 newly diagnosed patients with MM. A second and larger dataset involving 136 newly diagnosed patients with MM from IFM-2005 trial can be accessed via NCBI GSE ID: GSE39754. CD-138 purified plasma cells from 67 newly diagnosed patients with MM were profiled using Affymetrix Exon-1.0 ST microarray platform. Pre-processing and normalization of dataset was carried out using dChip (http://www.hsph.harvard.edu/cli/complab/dchip/exon.htm#expressio) and R package - aroma.affymetrx (http://www.aroma-project.org/vignettes/FIRMA-HumanExonArrayAnalsis). Patients subsequently received bortezomib based induction therapy, followed by autologus stem cell transplant. Post-induction treatment response is attached in metadata file.
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Project description:<h4><strong>BACKGROUND:</strong> Multiple myeloma is characterized by clonal proliferation of malignant plasma cells in the bone marrow that produce monoclonal immunoglobulins. N-glycosylation changes of these monoclonal immunoglobulins have been reported in multiple myeloma, but previous studies only detected limited serum N-glycan features.</h4><h4><strong>METHODS:</strong> Here, a more detailed study of the human serum N-glycome of 91 multiple myeloma patients and 51 controls was performed. We additionally analyzed sequential samples from patients (n = 7) which were obtained at different time points during disease development as well as 16 paired blood serum and bone marrow plasma samples. N-glycans were enzymatically released and measured by mass spectrometry after linkage specific derivatization of sialic acids.</h4><h4><strong>RESULTS:</strong> A decrease in both α2,3- and α2,6-sialylation, galactosylation and an increase in fucosylation within complex-type N-glycans were found in multiple myeloma patients compared to controls, as well as a decrease in difucosylation of diantennary glycans. The observed glycosylation changes were present in all ISS stages, including the 'low-risk' ISS I. In individual patients, difucosylation of diantennary glycans decreased with development of the disease. Protein N-glycosylation features from blood and bone marrow showed strong correlation. Moreover, associations of monoclonal immunoglobulin (M-protein) and albumin levels with glycan traits were discovered in multiple myeloma patients.</h4><h4><strong>CONCLUSIONS & GENERAL SIGNIFICANCE: </strong>In conclusion, serum protein N-glycosylation analysis could successfully distinguish multiple myeloma from healthy controls. Further studies are needed to assess the potential roles of glycan trait changes and the associations of glycans with clinical parameters in multiple myeloma early detection and prognosis.</h4>
2022-04-27 | MTBLS676 | MetaboLights