Identification of EGR2 and TGFB1 as Potential Immunoregulatory Biomarkers for Allergic Rhinitis: An Exploratory Bioinformatics and Pilot Validation Study.

BACKGROUND Allergic rhinitis (AR) is a common inflammatory disorder of the nasal mucosa triggered by allergens and characterized by sneezing, nasal congestion, and itching. This study aimed to identify and validate potential biomarkers associated with immune dysregulation in AR via bioinformatics analyses initiated with chemokine-related genes. MATERIAL AND METHODS AR-related datasets (GSE75011 and GSE50223) and 69 chemokine-related genes were analyzed via differential expression analysis and weighted gene co-expression network analysis to identify candidate genes. Random forest analysis was used to select optimal features. Expression analysis identified potential immunoregulatory biomarkers that were downregulated in AR samples. A nomogram incorporating these biomarkers was constructed as an exploratory tool to estimate individual AR probability and support future diagnostic model development. RESULTS Early growth response protein 2 (EGR2) and transforming growth factor-ß1 (TGFB1) were identified as chemokine-related biomarkers in AR. Immune infiltration analysis showed significant correlations between TGFB1 and M2 macrophages, as well as activated memory CD4+ T cells. Drug prediction identified tretinoin as a potential therapeutic agent targeting both biomarkers; molecular docking confirmed stable binding of the 3 top-ranked predicted drugs with TGFB1. Pilot reverse transcription-quantitative polymerase chain reaction analysis demonstrated downregulation of EGR2 and TGFB1 in AR samples, providing preliminary supportive evidence. Gene set enrichment analysis indicated involvement in the MAPK and p53 signaling pathways, suggesting roles in cell proliferation, apoptosis, cell cycle regulation, and stress responses. CONCLUSIONS EGR2 and TGFB1 offer potential immunoregulatory biomarkers for AR diagnosis and may provide preliminary insights into AR pathogenesis and potential treatment strategies.