Interaction between N6-methyladenosine and autophagy in the immune infiltration and subtype classification of thyroid eye disease

Abstract

Abstract Background:Thyroid eye disease (TED) is a chronic inflammatory autoimmune disease with a complex etiology. N6-methyladenosine (m6A) modification and autophagy were confirmed separately to be involved in the TED process. Increased evidence has shown that m6A is critical in regulating autophagy in various diseases. However, there is limited knowledge about the interactive effects of m6A modification and autophagy in TED. Our research aimed to investigate the effects of m6A modification and autophagy interactivity in TED. Results: We first identified dysregulation of five m6A regulators and 44 ARGs in TED patients compared to healthy controls. After correlation analysis, overlapping with the validated target genes from the RM2target database, and verification in our samples, FTO and BNIP3 were considered biomarkers for TED. Subsequently, based on dysregulated m6A regulators and ARGs separately, we classified 27 TED patients into two clusters, and the immune infiltration characteristics of clusters were further evaluated. Cluster-related differentially expressed genes were identified, and the enriched biological functions and pathways were elucidated. In addition, using two machine learning algorithms, we created a prediction model for TED patients with different molecular clusters. The nomogram, calibration curve, and decision curve analysis were performed to assess the performance of the predictive model. Conclusions: This study revealed that an interactive effect between FTO and BNIP3, suppressed FTO might downregulate the expression of BNIP3 in an m6A-dependent manner, inhibiting the autophagy and subsequently promoting the TED process. In addition, we constructed a nomogram model in predicting the TED. These results provide new insights into understanding the mechanism of TED.