Frontiers in Immunology (Oct 2022)
Common molecular mechanism and immune infiltration patterns of thoracic and abdominal aortic aneurysms
Abstract
BackgroundAortic disease (aortic aneurysm (AA), dissection (AD)) is a serious threat to patient lives. Little is currently known about the molecular mechanisms and immune infiltration patterns underlying the development and progression of thoracic and abdominal aortic aneurysms (TAA and AAA), warranting further research.MethodsWe downloaded AA (includes TAA and AAA) datasets from the GEO database. The potential biomarkers in TAA and AAA were identified using differential expression analysis and two machine-learning algorithms. The discrimination power of the potential biomarkers and their diagnostic accuracy was assessed in validation datasets using ROC curve analysis. Then, GSEA, KEGG, GO and DO analyses were conducted. Furthermore, two immuno-infiltration analysis algorithms were utilized to analyze the common immune infiltration patterns in TAA and AAA. Finally, a retrospective clinical study was performed on 78 patients with AD, and the serum from 6 patients was used for whole exome sequencing (WES).ResultsThe intersection of TAA and AAA datasets yielded 82 differentially expressed genes (DEGs). Subsequently, the biomarkers (CX3CR1 and HBB) were acquired by screening using two machine-learning algorithms and ROC curve analysis. The functional analysis of DEGs showed significant enrichment in inflammation and regulation of angiogenic pathways. Immune cell infiltration analysis revealed that adaptive and innate immune responses were closely linked to AA progression. However, neither CX3CR1 nor HBB was associated with B cell-mediated humoral immunity. CX3CR1 expression was correlated with macrophages and HBB with eosinophils. Finally, our retrospective clinical study revealed a hyperinflammatory environment in aortic disease. The WES study identified disease biomarkers and gene variants, some of which may be druggable.ConclusionThe genes CX3CR1 and HBB can be used as common biomarkers in TAA and AAA. Large numbers of innate and adaptive immune cells are infiltrated in AA and are closely linked to the development and progression of AA. Moreover, CX3CR1 and HBB are highly correlated with the infiltration of immune cells and may be potential targets of immunotherapeutic drugs. Gene mutation research is a promising direction for the treatment of aortic disease.
Keywords
