Construction of an Immune-Related Prognostic Signature and lncRNA‒miRNA-mRNA ceRNA Network in Acute Myeloid Leukaemia.

Abstract

The progression of acute myeloid leukaemia (AML) is influenced by the immune microenvironment in the bone marrow and dysregulated intracellular competing endogenous RNA (ceRNA) networks. Our study utilized data from UCSC Xena, Cancer Genome Atlas Program, Gene Expression Omnibus, Immunology Database and Analysis Portal. Using Cox regression analysis, we identified an immune-related prognostic signature. Genomic analysis of prognostic mRNA was conducted through Gene Set Cancer Analysis (GSCA), and a prognostic ceRNA network was constructed using the Encyclopedia of RNA Interactomes. Correlations between signature mRNAs and immune cell infiltration, checkpoints, and drug sensitivity were assessed using R software, GEPIA, and CellMiner, respectively. Adhering to the ceRNA hypothesis, we established a potential lncRNA/miRNA/mRNA regulatory axis. Our findings pinpointed nine immune-related prognostic mRNAs (KIR2DL1, CSRP1, APOBEC3G, CKLF, PLXNC1, PNOC, ANGPT1, IL1R2, and IL3RA). GSCA analysis revealed the impact of copy number variations and methylation on AML. The ceRNA network comprised 14 differentially expressed prognostic lncRNAs (DE-lncRNAs), six prognostic DE-miRNAs, and three prognostic immune-related IR-DEmRNAs. Correlation analyses linked these mRNA's expression to 22 immune cell types, six immune checkpoints, and potential sensitivity to 27 antitumor drugs. Finally, we identified a potential LINC00963/hsa-miR-431-5p/CSRP1 axis. This study offers innovative insights for AML diagnosis and treatment through a novel immune-related signature and ceRNA axis. Identified novel biomarkers, including two mRNAs (CKLF, PNOC), one miRNA (hsa-miR-323a-3p), and ten lncRNAs (SNHG25, LINC01857, AL390728.6, AC127024.5, Z83843.1, AP002884.1, AC007038.1, AC112512, AC020659.1, AC005921.3) present promising candidates as potential targets for precision medicine, contributing to the ongoing advancements in the field.