Abstract
In this study we analyzed gene co-expression networks of three immune-related skin diseases: cutaneous sarcoidosis (CS), discoid lupus erythematosus (DLE), and psoriasis. We propose that investigation of gene co-expression networks may provide insights into underlying disease mechanisms. Microarray expression data from two cohorts of patients with CS, DLE, or psoriasis skin lesions were analyzed. We applied weighted gene correlation network analysis (WGCNA) to construct gene-gene similarity networks and cluster genes into modules based on similar expression profiles. A module of interest that was preserved between datasets and corresponded with case/control status was identified. This module was related to immune activation, specifically leukocyte activation, and was significantly increased in both CS lesions and DLE lesions compared to their respective controls. Protein-protein interaction (PPI) networks constructed for this module revealed seven common hub genes between CS lesions and DLE lesions: TLR1, ITGAL, TNFRSF1B, CD86, SPI1, BTK, and IL10RA. Common hub genes were highly upregulated in CS lesions and DLE lesions compared to their respective controls in a differential expression analysis. Our results indicate common gene expression patterns in the immune processes of CS and DLE, which may have indications for future therapeutic targets and serve as Th1-mediated disease biomarkers. Additionally, we identified hub genes unique to CS and DLE, which can help differentiate these diseases from one another and may serve as unique therapeutic targets and biomarkers. Notably, we find common gene expression patterns in the immune processes of CS and DLE through utilization of WGCNA.
Highlights
Cutaneous sarcoidosis (CS), discoid lupus erythematosus (DLE), and psoriasis are immune-related cutaneous disorders with different pathologies and clinical presentations
Our findings suggest that there may be common gene expression patterns in the immune processes of cutaneous sarcoidosis (CS) and DLE
Since there were no significant differences between control and non-lesional skin (NLS), it appears that the gene dysregulation is confined to the sarcoidosis lesions
Summary
Cutaneous sarcoidosis (CS), discoid lupus erythematosus (DLE), and psoriasis are immune-related cutaneous disorders with different pathologies and clinical presentations. CS occurs in up to one third of patients with systemic sarcoidosis, an inflammatory disease characterized by non-caseating granulomas [1]. DLE can occur as a skin manifestation of systemic lupus erythematosus (SLE) in up to 20% of patients [2, 3]. While psoriasis was traditionally considered a Th1-mediated disease, recent studies suggests that psoriasis may be predominantly Th17-mediated [7]. Both CS and DLE may be predominantly Th1mediated diseases [8, 9]
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