Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Mar 8;21(1):182.
doi: 10.1186/s12967-023-03923-z.

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

Yingxi Li  1 , Lin Li  2 , Yao Tian  3 , Jing Luo  1 , Junkai Huang  1 , Litao Zhang  2 , Junling Zhang  2 , Xiaoxia Li  4 , Lizhi Hu  5
Affiliations

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

Yingxi Li et al. J Transl Med. .

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.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
The DEGs from lesioned psoriasis samples and non-lesioned skin samples represented as volcano plots (A) and heatmaps (B)
Fig. 2
Fig. 2
Functional enrichment analysis based on up-regulated genes of psoriasis. The molecular pathway enrichment by GSEA (A) and KEGG (B). C The disease enrichment by DOSE analysis
Fig. 3
Fig. 3
Identification of potential hub genes and its regulations. A Predicted potential upstream regulatory transcription factors of up-regulated genes in psoriasis. B PPI networks of 99 up-regulated genes in psoriasis. C The correlations of 5 hub genes by Pearson’s analysis. D–G Correlation of 5 hub genes expression with immune infiltration levels in psoriasis (D). Association of AHCY (E), PPIF (F) and PGD (G) expression with the number of infiltrating cells in psoriasis
Fig. 4
Fig. 4
The expression of 5 hub genes in psoriasis samples by IHC
Fig. 5
Fig. 5
Potential immune subtypes of psoriasis. A Venn diagram identifying 13 genes that were shared by immune-related genes and up-regulated genes in psoriasis. B, C The cumulative distribution function curve (B) and δ area (C) of immune-related genes in GSE14905 cohort. D The heatmap of sample clustering. Consensus matrix for k = 2, which was the optimal cluster number. E The t-SNE plot for the data set. C1, colored by red. C2, colored by blue. F The heatmap between hub genes and two immune subtypes of psoriasis. *P < 0.05; **P < 0.01; ***P < 0.001
Fig. 6
Fig. 6
Analysis of immune infiltration of subtype C1 and C2. A Heatmaps of correlation between 28 immune infiltrating cells and different immune subtypes of psoriasis. Exp, Expression. B Differential enrichment scores of relevant immune cell signatures in C1 and C2 subtypes. C Heatmaps of correlation between 28 immune infiltrating cells and 13 genes
Fig. 7
Fig. 7
Candidate drugs and its mechanism for each subtype of psoriasis. A, B Connectivity Map analysis showed 48 molecular pathways targeted by 34 compounds in C1 (A) and 20 biological pathways targeted by 19 compounds in C2 (B)
See this image and copyright information in PMC

References

    1. Singh R, Koppu S, Perche PO, Feldman SR. The cytokine mediated molecular pathophysiology of psoriasis and its clinical implications. Int J Mol Sci. 2021;22:12793. doi: 10.3390/ijms222312793. - DOI - PMC - PubMed
    1. Kim J, Moreno A, Krueger JG. The imbalance between type 17 T-cells and regulatory immune cell subsets in psoriasis vulgaris. Front Immunol. 2022;13:1005115. doi: 10.3389/fimmu.2022.1005115. - DOI - PMC - PubMed
    1. Boehncke WH, Schön MP. Psoriasis. Lancet. 2015;386:983–994. doi: 10.1016/S0140-6736(14)61909-7. - DOI - PubMed
    1. Langley RG, Elewski BE, Lebwohl M, Reich K, Griffiths CE, Papp K, Puig L, Nakagawa H, Spelman L, Sigurgeirsson B, et al. Secukinumab in plaque psoriasis–results of two phase 3 trials. N Engl J Med. 2014;371:326–338. doi: 10.1056/NEJMoa1314258. - DOI - PubMed
    1. Reich K, Nestle FO, Papp K, Ortonne JP, Evans R, Guzzo C, Li S, Dooley LT, Griffiths CE, Investigators Es Infliximab induction and maintenance therapy for moderate-to-severe psoriasis: a phase III, multicentre, double-blind trial. Lancet. 2005;366:1367–1374. doi: 10.1016/S0140-6736(05)67566-6. - DOI - PubMed

Publication types