Identification of Immunoregulatory Factors in the Development of Myeloproliferative Neoplasms by Bioinformatics
Myeloproliferative neoplasms(MPN)represent a group of chronic myeloproliferative disorders initiated by the hyperp-roliferation of hematopoietic stem cells,giving rise to conditions such as polycythemia vera,essential thrombocythemia,and pri-mary myelofibrosis.In both afflicted patients and murine models,the inflammatory response exhibits dysregulation,and an un-due inflammatory reaction serves to foster the initiation and progression of myeloproliferative tumors.A comprehensive explora-tion of the immunoinflammatory mechanisms in MPN is essential for the advancement of its treatment.To investigate the mecha-nism,we utilized gene expression profiling microarrays(accession number GSE174060)retrieved from the Gene Expression om-nibus database,including 50 patients with myeloproliferative tumor and 15 normal donors.Using limma analysis,1 269 differen-tially expressed genes(DEGs)were identified(|log2FC|≥0.5 and P.adjust<0.05),including 810 up-regulated genes and 459 down-regulated genes.We subsequently identified 128 immune-related genes,comprising 108 up-regulated genes and 20 down-regulat-ed genes.This selection was made by intersecting the set of differentially expressed genes with the set of immune-related genes.Notably,these genes were predominantly enriched in signaling pathways associated with the inflammatory response and chemo-taxis,as established through gene function annotation analysis.To gain insights into the interplay of these immune-related genes,we utilized Cytoscape software to construct protein interaction networks.This analysis uncovered two prominent modules:Module 1,comprising 11 nodes and 62 edges,and Module 2,consisting of 9 nodes and 36 edges.Additionally,we identified 10 critical immune-related HUB genes(IL1B,JAK2,CXCL10,ICAM1,CX3CR1,TLR4,MMP9,CD4,CCR1,LYN)using the Cytohub-ba plugin.The research further validated the importance of these HUB genes through gene expression analysis using the GSE103237 dataset.In conclusion,this study contributes to the identification of pivotal immune-inflammatory factors in MPN and enhances the understanding of the molecular mechanisms driving inflammation in MPN,providing a foundation for develop-ing targeted strategies and treatment approaches for MPN.
万方数据
维普
