TFE3 and TP53 were novel diagnostic biomarkers related to mitochondrial autophagy in chronic rhinosinusitis with nasal polyps.

BACKGROUND

Chronic rhinosinusitis with nasal polyps (CRSwNP) belongs to a subtype of Chronic rhinosinusitis which is a heterogeneous inflammatory condition. It has been reported that mitophagy may provide a new therapeutic option for CRSwNP.

METHODS

The GSE136825 (training dataset) and GSE179265 (validation dataset) were scoured from the Gene Expression Omnibus database. The candidate genes related to mitophagy were identified by differential expression analysis. Subsequently, the biomarkers were selected from the machine learning, Receiver Operating Characteristic curves, and expression level verification. A backpropagation (BP) neural network was generated to evaluate the diagnostic ability of biomarkers. In addition, the infiltration abundance of immune cells, potential drugs, and related ear-nose-throat (ENT) diseases were analyzed based on the biomarkers. Finally, qPCR analysis was performed to verify these biomarkers.

RESULTS

A total of 8 candidate genes were identified by overlapping 3,400 differentially expressed genes (DEGs) and 72 mitophagy-related genes Subsequently, TFE3 and TP53 were identified as biomarkers of CRSwNP, and the area under the curves (AUC) of the BP neural network was 0.74, which indicated that the biomarkers had excellent abilities. TFE3 and TP53 were co-enriched in the cancer pathway, cell cycle, endocytosis, etc. What's more, Macrophage and Immature dendritic cells had significant correlations with biomarkers. The drugs (Doxorubicin, Tetrachlorodibenzodioxin, etc.) and the ear-nose-throat diseases (hearing loss, sensorineural, tinnitus, etc.) related to biomarkers were predicted. Ultimately, qPCR results showed that the expression levels of TFE3 and TP53 in polyp tissue of CRSwNP were increased.

CONCLUSION

Overall, TFE3 and TP53 could be used as biomarkers or potential therapeutic targets to diagnose and treat CRSwNP.