Identification of three autophagy-related genes as diagnostic biomarkers and analysis of immune cell infiltration in ankylosing spondylitis patients

Abstract

Abstract Background Ankylosing spondylitis (AS) is a rheumatic immune disease that predominantly affects the sacroiliac joints and spinal joints, but the etiopathogenesis of AS remains unclear. The present research aimed to identify novel therapeutic targets and explore the molecular mechanism of AS via a bioinformatics approach. Methods Two microarray datasets (GSE25101 and GSE18781) were downloaded, and Gene Set Enrichment Analysis (GSEA) was used to analyze autophagy-related pathways. Autophagy-related genes (ARGs) were collected from the Human Autophagy-dedicated Database. The differentially expressed genes (DEGs) were screened with the limma package. Differentially expressed autophagy-related genes (DEARGs) were identified by intersecting the DEGs with the ARGs. Besides, GO-BP and KEGG enrichment analyses of DEARGs associated with AS were conducted by clusterProfiler package. Furthermore, hub genes among DEARGs were screened by Receiver operating characteristic (ROC) curve analysis. Finally, the expression of hub DEARGs were validated by GSE73754 dataset. Results GSEA results indicated that selective autophagy, programmed cell death, and endocytosis were involved in the occurrence and development of AS. A total of 10 DEARGs shared in the two datasets were identified. Besides, functional enrichment analysis results indicated these DEARGs were mainly enriched in mitophagy and autophagy. Three core DEARGs (PTEN, GABARAPL2, and PRKCQ) with AUC > 0.7 were confirmed to have the diagnostic value in AS. Immune cell infiltration analysis identified CD8 + T cells, NK cells, neutrophils, Tgd cells, Th1 cells, and Th2 cells as major participants in the AS development. Conclusions Overall, PTEN, GABARAPL2, and PRKCQ may be used as diagnostic biomarkers for AS. Besides, their relationships with immune cell infiltration will contribute to the development of immunotherapy in AS patients.