Network-based analysis of the molecular mechanisms of multiple myeloma and monoclonal gammopathy of undetermined significance
نویسندگان
چکیده
The present study aimed to reveal the molecular mechanisms of multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS). This was a secondary study on microarray dataset GSE80608, downloaded from the Gene Expression Omnibus database, which included 10 control samples, 10 MGUS samples and 10 MM samples. Differentially expressed genes (DEGs) were identified between control and MGUS samples, and between control and MM samples. A protein-protein interaction (PPI) network was built for studying the interactions between the DEGs. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis was performed for the genes in a gene co-expression network. A microRNA (miRNA/miR)-gene network was built to the evaluate possible the miRNAs and genes involved in the diseases. The present study identified 136 common upregulated DEGs and 165 common downregulated DEGs between MM and MGUS. Pathway enrichment analysis of the genes in the gene co-expression network revealed that the complement and coagulation cascades pathway was significantly enriched for certain complement and coagulation-associated genes. Endothelin-1 (EDN1) was significantly enriched in the hypoxia inducible factor-1 (HIF-1) and tumor necrosis factor signaling pathways. EDN1 was an important node in the PPI network, and a target gene of let-7e, let-7b and miR-19a in the miRNA-gene network. The results of the present study indicate that complement and coagulation-associated genes, the complement and coagulation cascades pathway, EDN1, let-7e, let-7b-5p, miR-19a, and the tumor necrosis factor and HIF-1 signaling pathways may all be implicated in MM and MGUS.
منابع مشابه
Monoclonal Gammopathy of Undetermined Significance with Metastatic Carcinoma – A Rare Presentation
The presence of a low level of M protein in the peripheral blood <3gm/dl which is below the required cut off for the diagnosis of plasma cell myeloma is known as monoclonal gammopathy of undetermined significance (MGUS). Elevated levels of serum M protein and detection of M band on serum protein electrophoresis (SPE) can occur in chronic diseases not related to B cell disorders and not always d...
متن کاملThe clinical relevance and management of monoclonal gammopathy of undetermined significance and related disorders: recommendations from the European Myeloma Network.
Monoclonal gammopathy of undetermined significance is one of the most common pre-malignant disorders. IgG and IgA monoclonal gammopathy of undetermined significance are precursor conditions of multiple myeloma; light-chain monoclonal gammopathy of undetermined significance of light-chain multiple myeloma; and IgM monoclonal gammopathy of undetermined significance of Waldenström's macroglobuline...
متن کاملThe spectrum of somatic mutations in monoclonal gammopathy of undetermined significance indicates a less complex genomic landscape than that in multiple myeloma
Monoclonal gammopathy of undetermined significance is a pre-malignant precursor of multiple myeloma with a 1% risk of progression per year. Although targeted analyses have shown the presence of specific genetic abnormalities such as IGH translocations, RB1 deletion, 1q gain, hyperdiploidy or RAS gene mutations, little is known about the molecular mechanism of malignant transformation. We perfor...
متن کاملNon Secretory Multiple Myeloma With HCV Infection: A Rare Case Entity
Multiple Myeloma is a neoplasm of B cell lineage characterized by excessive proliferation of abnormal plasma cells. It is characterized by a clinical pentad of 1) anemia, 2) a monoclonal protein in the serum or the urine or both, 3) bone leisons and or bone pain, 4) hypercalcemia >11.5g/dl and 5) renal insufficiency. Non secretory multiple myeloma is a rare variant of the classic form of multi...
متن کاملTranscriptome analysis reveals molecular profiles associated with evolving steps of monoclonal gammopathies.
A multistep model has been proposed of disease progression starting in monoclonal gammopathy of undetermined significance continuing through multiple myeloma, sometimes with an intermediate entity called smoldering myeloma, and ending in extramedullary disease. To gain further insights into the role of the transcriptome deregulation in the transition from a normal plasma cell to a clonal plasma...
متن کاملMonoclonal gammopathy of undetermined significance.
Monoclonal gammopathy of undetermined significance is not a benign condition. There is a significant increase in mortality associated with the risk of development of multiple myeloma and related disorders.
متن کامل