Feature genes identification and immune infiltration assessment in abdominal aortic aneurysm using WGCNA and machine learning algorithms.

OBJECTIVE

Abdominal aortic aneurysm (AAA) is a life-threatening vascular condition. This study aimed to discover new indicators for the early detection of AAA and explore the possible involvement of immune cell activity in its development.

METHODS

Sourced from the Gene Expression Omnibus, the AAA microarray datasets GSE47472 and GSE57691 were combined to generate the training set. Additionally, a separate dataset (GSE7084) was designated as the validation set. Enrichment analyses were carried out to explore the underlying biological mechanisms using Disease Ontology, Kyoto Encyclopedia of Genes and Genomes, and Gene Ontology. We then utilized weighted gene co-expression network analysis (WGCNA) along with 3 machine learning techniques: least absolute shrinkage and selection operator, support vector machine-recursive feature elimination, and random forest, to identify feature genes for AAA. Moreover, data were validated using the receiver operating characteristic (ROC) curve, with feature genes defined as those having an area under the curve above 85% and a -value below 0.05. Finally, the single sample gene set enrichment analysis algorithm was applied to probe the immune landscape in AAA and its connection to the selected feature genes.

RESULTS

We discovered 72 differentially expressed genes (DEGs) when comparing healthy and AAA samples, including 36 upregulated and 36 downregulated genes. Functional enrichment analysis revealed that the DEGs associated with AAA are primarily involved in inflammatory regulation and immune response. By intersecting the result of 3 machine learning algorithms and WGCNA, 3 feature genes were identified, including MRAP2, PPP1R14A, and PLN genes. The diagnostic performance of all these genes was strong, as revealed by the ROC analysis. A significant increase in 15 immune cell types in AAA samples was observed, based on the analysis of immune cell infiltration. In addition, the 3 feature genes show a strong linkage with different types of immune cells.

CONCLUSION

Three feature genes (MRAP2, PPP1R14A, and PLN) related to the development of AAA were identified. These genes are linked to immune cell activity and the inflammatory microenvironment, providing potential biomarkers for early detection and a basis for further research into AAA progression.