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فاطمه آتین، میثم مباشری

Background: Multiple Myeloma (MM) the neoplasm of bone marrow plasma cells constitutes approximately 10% of haematological malignancies worldwide and is the second most prevalent haematological cancer in developed countries. Despite the extended 5-year survival rates due to the recent advances in the treatment of this disease, patients still die mostly from their disease or treatment-induced complications. This study is aimed to conduct gene expression analysis of multiple myeloma patients which can assist in biomarker identification and discovering new targeted therapies. Methods: The GSE146649 microarray data was retrieved from genome expression omnibus (GEO). RMA was applied for the data normalisation. Differential gene expression (DGE) analysis was carried out by R/Bioconductor package. STRING was utilized for depicting the PPI network of highly overexpressed genes. Clustering analysis was performed using Cytoscape and Gephi software. Pathway enrichment analysis was carried out based on KEGG and Wikipathway databases to better understand the associated pathways. Results: A total number of 697 highly over expressed genes were identified. PPI network indicated 103 hub genes based on 3 standards (degree, closeness, betweenness). Clustering analysis dissected the network into 8 structural modules. Among the identified hub genes, SRC, EGFR, ITGB1, RSP9, PMSC are evident to play an integral role in the process and prognosis of multiple myeloma. The MM relevance of ITCH, GLI2, ERBB3, LGR4, MDM4 and PTP2 were also underscored and PPI network level. Calcium-RasGRP2, Th9/IL9, JAK-STAT, PI3K-AKT, c-AMP signalling pathway, NOTCH, CKAP4 mediated signalling pathway, NRF2, C-Kit isoforms, Renin-angiotensin, Fatty acid metabolism, SLE, CMV, HPV, Ulcerative colitis were identified as key pathways relevant to MM according to enrichment analysis. Conclusion: Our study found several hub genes and pathways involved in MM progression. Given that most of the highlighted genes and pathways are validated by available evidence, other genes and pathways with currently limited literature .documentation may contribute to future discovery of novel MM biomarkers or drug targets

Multiple myeloma, PPI network, biomarker, hub gene

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آتین، فاطمه، مباشری، میثم، 1404، آنالیز خوشه ها و شبکه ارتباط پروتئین-پروتئین در مالتیپل میلوما، کنگره بین المللی زیست پزشکی سرطان و سلولهای بنیادی، http://conf.sums.ac.ir/fa/archive_index.php?c=HN-icsbc1&aid=1514234