Identification of Novel Immune Subtypes and Potential Hub Genes of Patients with Psoriasis

Abstract

Background Psoriasis is a common, chronic and relapsing immune-related inflammatory dermal disease. Patients with psoriasis suffering from the recurrences is mainly caused by immnue response disorder. Thus, our study is aim to identify novel immnue subtypes and select targeted drugs for the precision therapy in different subtypes of psoriasis. Methods Differentially expressed genes of psoriasis were identified from the Gene Expression Omnibus database. Functional and disease enrichment were performed by Gene Set Enrichment Analysis and Disease Ontology Semantic and Enrichment analysis. Hub genes of psoriasis were selected from protein-protein interaction networks using Metascape database. The expression of hub genes were validated in human psoriasis samples by RT-qPCR and immunohistochemistry. Further, novel immune subtypes of psoriasis were identified by ConsensusClusterPlus package and its association with hub genes were calculated. Immune infiltration analysis were performed and its candidate drugs were evaluated by Connectivity Map analysis. Results 182 differentially expressed genes of psoriasis were identified from GSE14905 corhot, in which 99 genes were significantly up-regulated and 83 genes were down-regulated. We then conducted funtional and disease enrichment in up-regulated genes of psoriasis. Five potential hub genes of psoriasis were obtained, including SOD2, PGD, PPIF, GYS1 and AHCY. The high expression of hub genes were validated in human psoriasis samples. Notably, two novel immune subtypes of psoriasis were determined and defined as C1 and C2. Bioinformatic analysis showed C1 and C2 had different enrichment in immune infiltration cells. Further, candidate drugs and mechanism of action that applicable to different subtypes were evaluated. Conclusion Our study identified two novel immnue subtypes and five potential hub genes of psoriasis. These findings might give insight into the pathogenesis of psoriasis and provide effective immunotherapy regimens for the precise treatment of psoriasis.