Expression profile analysis reveals hub genes that are associated with immune system dysregulation in primary myelofibrosis

Abstract

Objection: Primary myelofibrosis (PMF) is a familiar chronic myeloproliferative disease with an unfavorable prognosis. The effect of infection on the prognosis of patients with PMF is crucial. Immune system dysregulation plays a central role in the pathophysiology of PMF. To date, very little research has been conducted on the molecular mechanism of immune compromise in patients with PMF. Methods: To explore potential candidate genes, microarray datasets GSE61629 and 26049 were obtained from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) between PMF patients and normal individuals were evaluated, gene function was measured and a series of hub genes were identified. Several significant immune cells were selected via cell type enrichment analysis. The correlation between hub genes and significant immune cells was determined. Results: A total of 282 DEGs were found, involving 217 upregulated genes and 65 downregulated genes. Several immune cells were found to be reduced in PMF, such as CD4 + T cells, CD4 + Tems, CD4 + memory T cells. Gene Ontology (GO) enrichment analysis of DEGs reflected that most biological processes were associated with immune processes. Six hub genes, namely, HP, MPO, MMP9, EPB42, SLC4A1, and ALAS2, were identified, and correlation analysis revealed that these hub genes have a negative correlation with immune cell abundance. Conclusions: Taken together, the gene expression profile of whole blood cells in PMF patients indicated a battery of immune events, and the DEGs and hub genes might contribute to immune system dysregulation.

Targeted Metabolomics Highlights Dramatic Antioxidant Depletion, Increased Oxidative/Nitrosative Stress and Altered Purine and Pyrimidine Concentrations in Serum of Primary Myelofibrosis Patients

“…Concomitant depletion of both compounds may seriously compromise the immune system, thereby creating optimal conditions that favor cancer insurgence and progression. To support this hypothesis, it is worth underlining that PMF patients often develop symptoms of autoimmune disorders and dysregulated immune system phenomena [42,43]. In addition, infections are the main causes of unfavorable prognosis and represent the cause of death in 10% of PMF patients [44].…”