Bioinformatics analysis and preliminary clinical validation of ITGA9 and NPTX2 as prognosis-related genes in acute myeloid leukemia

OBJECTIVE: To investigate the expression and clinical significance of integrin subunit alpha 9 (ITGA9) and neuronal pentraxin 2 (NPTX2) in acute myeloid leukemia (AML), and to evaluate their potential diagnostic and prognostic value. METHODS: Differentially expressed genes (DEGs) associated with AML prognosis were identified from the Gene Expression Omnibus (GEO) dataset (GSE12417), followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. The expression and prognostic relevance of candidate genes were further validated using The Cancer Genome Atlas (TCGA) dataset and the Xiantao Academic online platform. Correlations of ITGA9 and NPTX2 with immune-regulatory genes, immune checkpoint molecules, and immune cell infiltration were analyzed to explore their potential immune associations. Peripheral blood samples from 60 newly diagnosed AML patients and 50 healthy controls were collected for quantitative real-time PCR validation. Diagnostic and prognostic performances were assessed using receiver operating characteristic (ROC) curve and Kaplan-Meier survival analyses. RESULTS: Seven prognosis-related genes were identified, among which ITGA9 and NPTX2 were significantly upregulated in AML. ITGA9 and NPTX2 were predominantly involved in modulating signaling receptor functions and were primarily associated with the phosphatidylinositol 3-kinase-AKT (PI3K-Akt) signaling. Immune correlation analysis revealed that ITGA9 and NPTX2 were associated with multiple immune-regulatory and checkpoint molecules, indicating potential involvement in AML immune microenvironment modulation. Clinical validation confirmed that ITGA9 and NPTX2 were markedly overexpressed in the AML patients. ROC curve analysis demonstrated strong diagnostic efficacy for ITGA9 and NPTX2. Among the 60 AML patients followed up, 29 died, and the deceased group exhibited significantly higher ITGA9 and NPTX2 expression. High expression of ITGA9 and NPTX2 was associated with reduced relapse-free survival. CONCLUSION: ITGA9 and NPTX2 are significantly overexpressed in AML and are closely associated with poor prognosis. Their strong diagnostic performance suggests that these two genes may serve as potential biomarkers and therapeutic targets for AML.