Machine learning-based revelation of GABBR1 and IQGAP2 as candidate biomarkers of pulmonary arterial hypertension and their correlation with immune infiltration

Abstract

AbstractPulmonary arterial hypertension (PAH) is a pulmonary vascular disease with complex pathogenesis, and its intrinsic molecular mechanisms remain unclear. The aim of this study was to screen gene expression data from PAH patients, identify possible diagnostic indicators of PAH and to investigate the role of immune cell infiltration in the progression of PAH.This study made use of the gene expression dataset of PAH patients from the GEO database. R software was used to identify differentially expressed genes and perform functional enrichment analysis. The SVM-RFE, LASSO and Random Forest algorithms were then used to screen for PAH hub genes and validated in the peripheral blood and lung tissue datasets. Finally, the CIBERSORT algorithm was used to assess PAH lung tissue immune cell infiltration and to investigate the correlation between hub genes and immune cells.A total of 132 DEGs were screened in this study, which were centrally involved in the neuroreceptor-ligand activity pathway and associated with neurotransmission and hemoglobin complex. A total of 2 pivotal genes, GABBR1 and IQGAP2, were obtained by machine learning algorithms. The 2 pivotal genes had good predictive power as verified by ROC curves. Further immune infiltration analysis showed a decrease in T cells and an increase in the proportion of macrophages and dendritic cells in the lung tissue of PAH patients. The expression of GABBR1 was positively correlated with T cells and negatively correlated with macrophages and dendritic cells.In our study, we identified 2 potential diagnostic key genes: GABBR1 and IQGAP2. Our findings may provide a theoretical basis for the analysis of the underlying mechanisms of PAH and the development of targeted medicines.Highlight BoxKey findingsWe identified 2 potential key genes of PAH, GABBR1 and IQGAP2.What is known and what is new?Sympathetic hyperexcitability as well as immune responses are closely associated with the development of PAH, and pulmonary vascular hyperplasia is a key pathogenetic mechanism of PAH.Important biomarkers related to neuroreceptors and immune responses in PAH lung tissue have not been identified, while our study identified GABBR1 as a key neuroreceptor and immune cell regulator in PAH. IQGAP2 could be a new hotspot direction for pulmonary vascular remodeling.What is the implication, and what should change now?GABBR1 and IQGAP2 may be potential therapeutic targets for PAH. The new horizon provided by this study will provide some reference for subsequent PAH studies.