Novel diagnostic biomarkers regulating macrophages autophagy in ischemic cardiomyopathy: An analysis integrating bulk RNA sequencing with single-cell RNA sequencing

Macrophage autophagy plays a pivotal role in ischemia cardiomyopathy (ICM). However, the underlying mechanisms and macrophage autophagy-related biomarkers in ICM have not been elucidated. Therefore, this study was designed to explore novel macrophage autophagy-related biomarkers for ICM. The autophagy-related genes were downloaded from the Human Autophagy Modulator and intersected with the differentially expressed genes (DEGs) of GSE46224 identified with "limma" package in R to obtain the autophagy-related DEGs. Immune infiltration analysis showed that macrophages were the dominant immune cells in ICM tissue. Then the macrophage autophagy-related DEGs were identified using the weighted gene co-expression network analysis (WGCNA). A total of six hub genes were obtained from the PPI network. All of the hub genes showed specific diagnostic significance with AUCs higher than 0.7, as also validated in the external dataset GSE116250. RT-qPCR was conducted to detect the mRNA expression levels of hub genes in vivo ICM rat model. Single-cell RNA sequencing analysis was also performed to investigate gene expression profiles. Our study explored the macrophage autophagy-related biomarkers and their relative pathways in ICM, provided novel diagnostic biomarkers for ICM, and gave new insight into the progression mechanism of ICM.