H1FX as a novel biomarker linking pan-apoptosis to immune dysregulation in allergic rhinitis

Allergic rhinitis (AR), a major subtype of rhinitis, is characterized by dysregulated apoptosis in the nasal mucosa, a process intrinsically correlated with its inflammatory pathology. The aim of this study was to identify pan-apoptosis-related genes with diagnostic and therapeutic relevance in AR.

We analyzed AR-related datasets (GSE75011 and GSE50223) from Gene expression Omnibus (GEO) database. Differentially expressed genes (DEGs) from GSE75011 were intersected with pan-apoptosis-related genes identified by WGCNA. Biomarkers closely associated with AR progression were screened applying LASSO and Recursive Feature Elimination (RFE). Functional enrichment was assessed via GSEA, and single-sample GSEA (ssGSEA) was utilized to analyze the association between immune cell infiltration and the biomarkers. In vitro assays were carried out to further elucidate the role of H1FX in an AR model.

DEGs were mainly enriched in IL-17 signaling pathway and MAPK signaling pathway. H1FX was identified as a key pan-apoptosis-related biomarker, with an AUC > 0.7 in ROC analysis. GSEA revealed differential enrichment of VEGF signaling pathway, MAPK signaling pathway, and Spliceosome and HALLMARK_G2M_CHECKPOINT between high and low expression groups of H1FX. ssGSEA analysis showed that H1FX expression was positively linked to Activated B cells, Central memory CD4 T cells, and significantly negatively correlated with Activated CD4 T cells in AR. Cellular assays confirmed that H1FX regulated proliferation and apoptosis in the AR model.

Integrating computational analyses and experimental validation, we identified H1FX as a pivotal regulator of pan-apoptosis and inflammatory responses in AR, highlighting its potential as a diagnostic biomarker and therapeutic target.