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Bioinformatics Analysis of Key Genes and Pathways Associated with Thrombosis in Essential Thrombocythemia.

ABSTRACT: BACKGROUND Essential thrombocythemia (ET) is a form of chronic myeloproliferative neoplasm (MPN), and thrombosis is an important complication. This study aimed to use bioinformatics analysis to identify differentially expressed genes (DEGs) in ET associated thrombosis. MATERIAL AND METHODS Two datasets were identified from the Gene Expression Omnibus (GEO) database to investigate the expression profiles in ET. The GSE103176 dataset included 24 patients with ET and 15 healthy individuals with samples from CD34+ bone marrow cells. The GSE54644 dataset included 47 patients with ET and 11 healthy individuals with samples from peripheral neutrophils. GEO2R was used to screen DEGs, followed by over-representation analysis. Protein-protein interaction (PPI) network analysis and module analysis were performed using the STRING database and Cytoscape software. Hub genes were identified using the cytoHubba Cytoscape plugin, and maximal clique centrality (MCC) was identified. The MCODE Cytoscape plugin was used to identify network clusters, or highly interconnected regions. RESULTS There were 586 and 392 DEGs identified from the GSE103176 and GSE54644 datasets, respectively. The upregulated DEGs for CD34+ cells were predominantly enriched for granulocyte activation or related pathways for biological process (BP), and secretory vesicle for the cellular component (CC). The top hub genes within CD34+ cells included CXCL1, CAMP, HP, MMP8, PTX3, ORM1, LYZ, LTF, PGLYRP1, and OLFM4. CONCLUSIONS Bioinformatics analysis identified DEGs and hub genes that interacted with CD34+ cells and neutrophils that may predict an increased risk of thrombosis in patients with ET. These preliminary findings should be validated using next-generation sequencing (NGS) and clinical studies.

SUBMITTER: Guo C

PROVIDER: S-EPMC6911306 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Bioinformatics Analysis of Key Genes and Pathways Associated with Thrombosis in Essential Thrombocythemia.

Guo Chao C Li Zhenling Z

Medical science monitor : international medical journal of experimental and clinical research 20191205

BACKGROUND Essential thrombocythemia (ET) is a form of chronic myeloproliferative neoplasm (MPN), and thrombosis is an important complication. This study aimed to use bioinformatics analysis to identify differentially expressed genes (DEGs) in ET associated thrombosis. MATERIAL AND METHODS Two datasets were identified from the Gene Expression Omnibus (GEO) database to investigate the expression profiles in ET. The GSE103176 dataset included 24 patients with ET and 15 healthy individuals with sam ...[more]

PMID: 31801935

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Project description:IntroductionEssential thrombocytosis (ET) is a group of myeloproliferative neoplasms characterized by abnormal proliferation of platelet and megakaryocytes. Research on potential key genes and novel regulatory markers in essential thrombocythemia (ET) is still limited.MethodsDownloading array profiles from the Gene Expression Omnibus database, we identified the differentially expressed genes (DEGs) through comprehensive bioinformatic analysis. GO, and REACTOME pathway enrichment analysis was used to predict the potential functions of DEGs. Besides, constructing a protein-protein interaction (PPI) network through the STRING database, we validated the expression level of hub genes in an independent cohort of ET, and the transcription factors (TFs) were detected in the regulatory networks of TFs and DEGs. And the candidate drugs that are targeting hub genes were identified using the DGIdb database.ResultsWe identified 63 overlap DEGs that included 21 common up-regulated and 42 common down-regulated genes from two datasets. Functional enrichment analysis shows that the DEGs are mainly enriched in the immune system and inflammatory processes. Through PPI network analysis, ACTB, PTPRC, ACTR2, FYB, STAT1, ETS1, IL7R, IKZF1, FGL2, and CTSS were selected as hub genes. Interestingly, we found that the dysregulated hub genes are also aberrantly expressed in a bone marrow cohort of ET. Moreover, we found that the expression of CTSS, FGL2, IKZF1, STAT1, FYB, ACTR2, PTPRC, and ACTB genes were significantly under-expressed in ET (P<0.05), which is consistent with our bioinformatics analysis. The ROC curve analysis also shows that these hub genes have good diagnostic value. Besides, we identified 4 TFs (SPI1, IRF4, SRF, and AR) as master transcriptional regulators that were associated with regulating the DEGs in ET. Cyclophosphamide, prednisone, fluorouracil, ruxolitinib, and lenalidomide were predicted as potential candidate drugs for the treatment of ET.DiscussionThese dysregulated genes and predicted key regulators had a significant relationship with the occurrence of ET with affecting the immune system and inflammation of the processes. Some of the immunomodulatory drugs have potential value by targeting ACTB, PTPRC, IL7R, and IKZF1 genes in the treatment of ET.

Project description:Breast cancer (BC) is the leading malignancy in women worldwide, yet relatively little is known about the genes and signaling pathways involved in BC tumorigenesis and progression. The present study aimed to elucidate potential key candidate genes and pathways in BC. Five gene expression profile data sets (GSE22035, GSE3744, GSE5764, GSE21422 and GSE26910) were downloaded from the Gene Expression Omnibus (GEO) database, which included data from 113 tumorous and 38 adjacent non?tumorous tissue samples. Differentially expressed genes (DEGs) were identified using t?tests in the limma R package. These DEGs were subsequently investigated by pathway enrichment analysis and a protein?protein interaction (PPI) network was constructed. The most significant module from the PPI network was selected for pathway enrichment analysis. In total, 227 DEGs were identified, of which 82 were upregulated and 145 were downregulated. Pathway enrichment analysis results revealed that the upregulated DEGs were mainly enriched in 'cell division', the 'proteinaceous extracellular matrix (ECM)', 'ECM structural constituents' and 'ECM?receptor interaction', whereas downregulated genes were mainly enriched in 'response to drugs', 'extracellular space', 'transcriptional activator activity' and the 'peroxisome proliferator?activated receptor signaling pathway'. The PPI network contained 174 nodes and 1,257 edges. DNA topoisomerase 2?a, baculoviral inhibitor of apoptosis repeat?containing protein 5, cyclin?dependent kinase 1, G2/mitotic?specific cyclin?B1 and kinetochore protein NDC80 homolog were identified as the top 5 hub genes. Furthermore, the genes in the most significant module were predominantly involved in 'mitotic nuclear division', 'mid?body', 'protein binding' and 'cell cycle'. In conclusion, the DEGs, relative pathways and hub genes identified in the present study may aid in understanding of the molecular mechanisms underlying BC progression and provide potential molecular targets and biomarkers for BC.

Dataset Information

Bioinformatics Analysis of Key Genes and Pathways Associated with Thrombosis in Essential Thrombocythemia.

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Bioinformatics Analysis of Key Genes and Pathways Associated with Thrombosis in Essential Thrombocythemia.

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