Autophagy-related genes are potential diagnostic biomarkers for dermatomyositis

Dermatomyositis (DM) is an autoimmune disease mainly diagnosed by its symptoms and a physical examination, with only some subtypes of DM showing clear molecular changes. To date, few biomarkers have been identified to assess DM progression. Autophagy-related genes have been significantly correlated with inflammation, several types of autoimmune diseases, and the immune response, but few studies have explored the role of autophagy-related genes in DM. Therefore, this study aimed to investigate the roles of autophagy-related genes in DM.

We collected three datasets of dermatomyositis-related transcriptome from the Gene Expression Omnibus (GEO) database: GSE1551, GSE46239, and GSE143323 and analyzed the differentially expressed genes (DEGs). We also conducted functional enrichment analyses with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. To explore whether the autophagy-related genes were differentially expressed in DM compared with normal samples, we performed an intersection between the DEGs and autophagy-related genes obtained from the Human Autophagy Database (HADb, http://www.autophagy.lu/). Finally, we used selected autophagy-related genes as biomarkers for diagnosing and analyzing the correlation with immune cell infiltration.

Our results showed that 143 genes were upregulated, and 14 were downregulated in the DM samples compared with healthy samples. The functional enrichment analysis revealed that these DEGs played a significant role in the type I interferon signaling pathway, cytokine activity, chemokine activity, double-stranded RNA binding, and blood microparticles. The intersection results identified CCL2, CDKN1A, FOS, MYC, and TNFSF10 as the primary autophagy-related genes in DM. All showed significantly increased expressions in DM samples compared with healthy samples. We were also curious to investigate immune cell infiltration in DM. Our results showed that the selected autophagy-related genes significantly influenced the infiltration of multiple immune cells, such as B cells, macrophages, and natural killer cells. Finally, we assessed the diagnostic sensitivity of CCL2, CDKN1A, FOS, MYC, and TNFSF10 for DM. The results showed the area under the curve (AUC) values of the ROC were 0.855, 0.889, 0.744, 0.826, and 0.816, respectively. The combined genes' diagnostic AUC value was 0.951.

CCL2, CDKN1A, FOS, MYC, and TNFSF10 are potential diagnostic biomarkers for DM.