Key genes distinguishing acute and chronic immune thrombocytopenia identified through bioinformatic analysis

Abstract

Objective: Immune thrombocytopenia (ITP) is an autoimmune hemorrhagic disorder characterized by decreased platelet count or impaired platelet production. This study employed bioinformatics approaches to analyze gene expression differences among the acute phase (ACU), progressive phase (PRO), and chronic phase (CHR) of ITP.

Methods: The microarray expression analysis dataset GSE23754 from the GEO database was performed. Based on the whole blood transcriptomic data of ITP patients during acute, progressive, and chronic phases, the patients were divided into three groups. GEO2R was used to perform pairwise comparisons of the data among the three groups, identifying three pairs of differentially expressed genes (DEGs) that represent distinct groups. These pairs of DEGs were further cross-compared to select DEGs unique to each stage. Subsequently, tissue specificity analysis, functional enrichment analysis, PPI network interaction analysis, and visualization were conducted.

Results: A total of 62 DEGs were identified in the ACU vs. PRO comparison (2 upregulated, 60 downregulated), 15 DEGs in the CHR vs. PRO comparison (3 upregulated, 12 downregulated), and 26 DEGs in the ACU vs. CHR comparison (1 upregulated, 25 downregulated). There were 10 downregulated genes, including SLC25A37, in the ACU phase; 5 upregulated genes, including VNN1, in the PRO phase; and ALAS2 (regulated by differential loci) and SLC23A2 in the CHR phase. Functional analysis revealed that the ACU phase was predominantly associated with innate immunity, inflammatory responses, and hematopoietic dysfunction, whereas the PRO and CHR phases were primarily linked to metabolic disorders. Protein-protein interaction (PPI) network analysis further untangled key pathways involved in disease progression. The ACU to PRO transition was mediated by the FCGR2B pathway; the ACU to CHR transition was associated with the ACSL1 pathway; and the PRO to CHR transition was regulated by the ALAS2-HBG1 pathway.

Conclusion: Differences in gene expression across the ACU, PRO, and CHR pathological stages may be associated with the pathophysiology of ITP at distinct disease phases. The ALAS2 gene exhibited differential expression in all three pathological stages, suggesting its potential role as a key biomarker in ITP pathogenesis. These findings provide a molecular basis for targeted therapy in ITP.