Autophagy-Related Genes Are Involved in the Progression and Prognosis of Asthma and Regulate the Immune Microenvironment
Fan Yang, Jingwei Kong, Yuhan Zong, Zhuqing Li, Mingsheng Lyu, Wanyang Li, Wenle Li, Haoyue Zhu, Shunqi Chen, Xiaoshan Zhao, Ji Wang
Abstract
Background Autophagy has been proven to play an important role in the pathogenesis of asthma and the regulation of the airway epithelial immune microenvironment. However, a systematic analysis of the clinical importance of autophagy-related genes (ARGs) regulating the immune microenvironment in patients with asthma remains lacking. Methods Clustering based on the k-means unsupervised clustering method was performed to identify autophagy-related subtypes in asthma. ARG-related diagnostic markers in low-autophagy subtypes were screened, the infiltration of immune cells in the airway epithelium was evaluated by the CIBERSORT, and the correlation between diagnostic markers and infiltrating immune cells was analyzed. On the basis of the expression of ARGs and combined with asthma control, a risk prediction model was established and verified by experiments. Results A total of 66 differentially expressed ARGs and 2 subtypes were identified between mild to moderate and severe asthma. Significant differences were observed in asthma control and FEV1 reversibility between the two subtypes, and the low-autophagy subtype was closely associated with severe asthma, energy metabolism, and hormone metabolism. The autophagy gene SERPINB10 was identified as a diagnostic marker and was related to the infiltration of immune cells, such as activated mast cells and neutrophils. Combined with asthma control, a risk prediction model was constructed, the expression of five risk genes was supported by animal experiments, was established for ARGs related to the prediction model. Conclusion Autophagy plays a crucial role in the diversity and complexity of the asthma immune microenvironment and has clinical value in treatment response and prognosis.