In silico identification and experimental validation of shared genes and exploration of molecular links between type...

Asthma, a complex disease, is categorized into type 2 (T2) and non-type 2 (non-T2) molecular endotypes. Growing evidence supports the overlap between endotypes and highlights a complex interplay among multiple inflammatory cell types. Combined inflammatory disease is particularly challenging to treat. Building on the background of overlapping asthma endotypes, the goal of this research was to explore common gene signatures and the underlying molecular mechanisms across different asthma subtypes.

Transcriptomics data of bronchial biopsy samples were sourced from the Gene Expression Omnibus (GEO) and intersected to identify common genes in T2 and non-T2 Asthma. Gene ontology, pathway enrichment, protein-protein interaction, immune infiltration, and single-cell analysis were used to explore the roles of these genes. Finally, common genes in T2 and non-T2 asthma mice models were verified by RT-qPCR.

Five upregulated common genes (MS4A2, TPSAB1, FCER1A, TFF3, TSPAN13) were identified. These genes showed good diagnostic accuracy for both T2 and non-T2 asthma. Gene Set Enrichment Analysis (GSEA) analyses revealed involvement of these genes in the immune and inflammatory response. Moreover, we found that both T2 and non-T2 asthma exhibit similar patterns of immune cell infiltration, such as mast cells, suggesting that mast cell activation can span different inflammatory phenotypes. Consistently, qRT-PCR analysis confirmed that the five genes were upregulated in both T2 and non-T2 asthma, aligning with the bioinformatic predictions.

This study revealed common genes and similar immune cell infiltration microenvironments in both T2 and non-T2 asthma. These findings may provide new insights for future studies on molecular mechanisms.