Identification of novel immune subtypes and potential hub genes of patients with psoriasis

Yingxi Li; Lin Li; Yao Tian; Jing Luo; Junkai Huang; Litao Zhang; Junling Zhang; Xiaoxia Li; Lizhi Hu

doi:10.1186/s12967-023-03923-z

Identification of novel immune subtypes and potential hub genes of patients with psoriasis

J Transl Med. 2023 Mar 8;21(1):182. doi: 10.1186/s12967-023-03923-z.

Authors

Yingxi Li¹, Lin Li², Yao Tian³, Jing Luo¹, Junkai Huang¹, Litao Zhang², Junling Zhang², Xiaoxia Li⁴, Lizhi Hu⁵

Affiliations

¹ Immunology Department, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Medical University, Tianjin, 300070, China.
² Department of Dermatology, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin, 300120, China.
³ Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, 300052, China.
⁴ Immunology Department, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Medical University, Tianjin, 300070, China. lilian_lxx@126.com.
⁵ Immunology Department, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Medical University, Tianjin, 300070, China. lizhihu@tmu.edu.cn.

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 immune response disorder. Thus, our study is aimed to identify novel immune 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 was 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 was performed, and its candidate drugs were evaluated by Connectivity Map analysis.

Results: 182 differentially expressed genes of psoriasis were identified from GSE14905 cohort, in which 99 genes were significantly up-regulated and 83 genes were down-regulated. We then conducted functional 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 was 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 cells. Further, candidate drugs and mechanism of action that applicable to different subtypes were evaluated.

Conclusions: Our study identified two novel immune 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.

Keywords: Bioinformatic analysis; Hub genes; Immune landscape; Immune subtypes; Psoriasis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Computational Biology
Databases, Factual
Drug Delivery Systems
Gene Expression Profiling
Humans
Immunotherapy
Psoriasis* / genetics