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 immune response disorder. Thus, our study is aimed to identify novel immune subtypes and select targeted drugs for t...

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Main Authors: Yingxi Li, Lin Li, Yao Tian, Jing Luo, Junkai Huang, Litao Zhang, Junling Zhang, Xiaoxia Li, Lizhi Hu
Format: Article
Language:English
Published: BMC 2023-03-01
Series:Journal of Translational Medicine
Subjects:
Online Access:https://doi.org/10.1186/s12967-023-03923-z
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author Yingxi Li
Lin Li
Yao Tian
Jing Luo
Junkai Huang
Litao Zhang
Junling Zhang
Xiaoxia Li
Lizhi Hu
author_facet Yingxi Li
Lin Li
Yao Tian
Jing Luo
Junkai Huang
Litao Zhang
Junling Zhang
Xiaoxia Li
Lizhi Hu
author_sort Yingxi Li
collection DOAJ
description 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.
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spelling doaj.art-9f73812ff1c64514bd709efe0066c58f2023-03-22T12:14:10ZengBMCJournal of Translational Medicine1479-58762023-03-0121111210.1186/s12967-023-03923-zIdentification of novel immune subtypes and potential hub genes of patients with psoriasisYingxi Li0Lin Li1Yao Tian2Jing Luo3Junkai Huang4Litao Zhang5Junling Zhang6Xiaoxia Li7Lizhi Hu8Immunology Department, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Medical UniversityDepartment of Dermatology, Tianjin Academy of Traditional Chinese Medicine Affiliated HospitalDepartment of General Surgery, Tianjin Medical University General HospitalImmunology Department, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Medical UniversityImmunology Department, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Medical UniversityDepartment of Dermatology, Tianjin Academy of Traditional Chinese Medicine Affiliated HospitalDepartment of Dermatology, Tianjin Academy of Traditional Chinese Medicine Affiliated HospitalImmunology Department, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Medical UniversityImmunology Department, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Medical UniversityAbstract 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.https://doi.org/10.1186/s12967-023-03923-zPsoriasisImmune landscapeHub genesImmune subtypesBioinformatic analysis
spellingShingle Yingxi Li
Lin Li
Yao Tian
Jing Luo
Junkai Huang
Litao Zhang
Junling Zhang
Xiaoxia Li
Lizhi Hu
Identification of novel immune subtypes and potential hub genes of patients with psoriasis
Journal of Translational Medicine
Psoriasis
Immune landscape
Hub genes
Immune subtypes
Bioinformatic analysis
title Identification of novel immune subtypes and potential hub genes of patients with psoriasis
title_full Identification of novel immune subtypes and potential hub genes of patients with psoriasis
title_fullStr Identification of novel immune subtypes and potential hub genes of patients with psoriasis
title_full_unstemmed Identification of novel immune subtypes and potential hub genes of patients with psoriasis
title_short Identification of novel immune subtypes and potential hub genes of patients with psoriasis
title_sort identification of novel immune subtypes and potential hub genes of patients with psoriasis
topic Psoriasis
Immune landscape
Hub genes
Immune subtypes
Bioinformatic analysis
url https://doi.org/10.1186/s12967-023-03923-z
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