Anti-TNF- αtreatment-related pathways and biomarkers revealed by transcriptome analysis in Chinese psoriasis patients

Abstract

Background Anti-tumor necrosis factor alpha (TNF- α ) therapy has made a significant impact on treating psoriasis. Despite these agents being designed to block TNF- α activity, their mechanism of action in the remission of psoriasis is still not fully understood at the molecular level. Results To better understand the molecular mechanisms of Anti-TNF- α therapy, we analysed the global gene expression profile (using mRNA microarray) in peripheral blood mononuclear cells (PBMCs) that were collected from 6 psoriasis patients before and 12 weeks after the treatment of etanercept. First, we identified 176 differentially expressed genes (DEGs) before and after treatment by using paired t-test. Then, we constructed the gene co-expression modules by weighted correlation network analysis (WGCNA), and 22 co-expression modules were found to be significantly correlated with treatment response. Of these 176 DEGs, 79 DEGs (M_DEGs) were the members of these 22 co-expression modules. Of the 287 GO functional processes and pathways that were enriched for these 79 M_DEGs, we identified 30 pathways whose overall gene expression activities were significantly correlated with treatment response. Of the original 176 DEGs, 19 (GO_DEGs) were found to be the members of these 30 pathways, whose expression profiles showed clear discrimination before and after treatment. As expected, of the biological processes and functionalities implicated by these 30 treatment response-related pathways, the inflammation and immune response was the top pathway in response to etanercept treatment, and some known TNF- α related pathways, such as molting cycle process, hair cycle process, skin epidermis development, regulation of hair follicle development, were implicated. Furthermore, additional novel pathways were also suggested, such as heparan sulfate proteoglycan metabolic process, vascular endothelial growth factor production, whose transcriptional regulation may mediate the response to etanercept treatment. Conclusion Through global gene expression analysis in PBMC of psoriasis patient and subsequent co-expression module based pathway analyses, we have identified a group of functionally coherent and differentially expressed genes (DEGs) and related pathways, which has not only provided new biological insight about the molecular mechanism of anti-TNF- α treatment, but also identified several genes whose expression profiles can be used as potential biomarkers for anti-TNF- α treatment response in psoriasis. Electronic supplementary material The online version of this article (10.1186/s12918-019-0698-7) contains supplementary material, which is available to authorized users.

Review—Current Concepts in Inflammatory Skin Diseases Evolved by Transcriptome Analysis: In-Depth Analysis of Atopic Dermatitis and Psoriasis

“…Recently, a Th2/Th17 profile was shown for a poison ivy ACD response in mice compared to a oxazolone-induced Th1-prominent polarization. Poison ivy ACD is in contrast to many other established antigens highly relevant in the human disease [130]. Therefore, the classical view of Th1/Th2-skewed profiles shifted toward a more prominent role of the Th17 axis.…”

“…Non-histaminergic itch is additionally important in allergic contact dermatitis potentially mediated via thymic stromal lymphopoietin (TSLP) [130]. Given the allergen-dependent immune response characteristics which are discussed in this review, allergen-specific murine models are needed in translational research to reach high validity.…”

“…Recently, Liu et al, introduced a poison ivy-based model (urushiol as the active compound). Thereby, they used a patient-relevant allergen [130].…”

Genome-wide association analysis of anti-TNF-α treatment response in Chinese patients with psoriasis

“…Increased expression of SDC3 has been shown on endothelia in rheumatoid arthritis and psoriasis arthritis synovium comparing to normal synovium, which is thought to have roles in angiogenesis, chemokine presentation and leukocytes extravasation (Patterson et al, 2008). Furthermore, we recently identified several pathways and functional processes including HSPG and VEGF production which are correlated with anti-TNF-a treatment (Liu et al, 2019). Therefore, SDC3 has the possibility to be a crucial part in the pathogenesis of psoriasis and influence the therapeutic response in psoriasis.…”

Weighted gene coexpression network and experimental analyses identify lncRNA SPRR2C as a regulator of the IL-22-stimulated HaCaT cell phenotype through the miR-330/STAT1/S100A7 axis

“…For the identification of a biomarker, screening based on WGCNA achieved a better validation rate than screening based on differential expression analysis. Since its development, WGCNA has been successfully used in multiple biological environments and has achieved a series of research results in psoriasis 9 , 16 – 19 .…”