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Expanding the psoriasis disease profile: interrogation of the skin and serum of patients with moderate-to-severe psoriasis.

Suárez-Fariñas M, Li K, Fuentes-Duculan J, Hayden K, Brodmerkel C, Krueger JG - J. Invest. Dermatol. (2012)

Bottom Line: This new analysis identified 4,175 probe sets (representing 2,725 unique known genes) as being differentially expressed in psoriasis lesions compared with matched biopsies of non-lesional skin when the following criteria were applied: >2-fold change and false discovery rate <0.05.These probe sets represent the largest and most comprehensive set of genes defining psoriasis at the molecular level and within the previously unidentified genes, a link to functional pathways associated with metabolic diseases/diabetes and to cardiovascular risk pathways is identified.We identified linkage of functional pathways in lesional skin associated with metabolic diseases/diabetes and cardiovascular risk with those pathways overexpressed in the serum, suggesting a potential linkage between altered gene transcription in the skin and comorbidities commonly seen in patients with moderate-to-severe psoriasis.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Investigative Dermatology, Rockefeller University, New York, New York, USA.

ABSTRACT
Psoriasis is a complex disease with an expanding definition of its pathological features. We sought to expand/refine the psoriasis transcriptome using 85 paired lesional and non-lesional samples from a cohort of patients with moderate-to-severe psoriasis vulgaris who were not receiving active psoriasis therapy. This new analysis identified 4,175 probe sets (representing 2,725 unique known genes) as being differentially expressed in psoriasis lesions compared with matched biopsies of non-lesional skin when the following criteria were applied: >2-fold change and false discovery rate <0.05. These probe sets represent the largest and most comprehensive set of genes defining psoriasis at the molecular level and within the previously unidentified genes, a link to functional pathways associated with metabolic diseases/diabetes and to cardiovascular risk pathways is identified. In addition, we profiled the serum of moderate-to-severe psoriatics compared with healthy controls to assess the overlap of overexpressed lesional genes with overexpressed systemic proteins. We identified linkage of functional pathways in lesional skin associated with metabolic diseases/diabetes and cardiovascular risk with those pathways overexpressed in the serum, suggesting a potential linkage between altered gene transcription in the skin and comorbidities commonly seen in patients with moderate-to-severe psoriasis.

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The transcriptome of moderate-to-severe psoriasis. (a) Heatmap of differentially expressed genes (DEGs). Unsupervised clustering of lesional (LS) versus non-lesional (NL) DEGs. (b) Scatter plot of the estimated fold change (log2 scale) by real-time reverse transcriptase PCR (RT-PCR, x-axis) and gene array (y-axis) for a selected group of 50 genes (see Table 3). Gray lines outline the two-fold change (FCH) regions. Stars and bullets represent two different low-density cards. Red shows confirmed genes. Classical linear regression analysis (red line) shows a slight compression of FCHs by gene array. Pearson's (r) and Spearman's (ρ) correlation values are presented along with P-values. (c) Venn diagram comparing genes (blue numbers: downregulated genes; red numbers: upregulated genes) identified in this study with those of two published studies employing the same Affymetrix HG U133 Plus 2.0 arrays using the same cutoff criteria (false discovery rate <0.05, FCH>2).
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fig1: The transcriptome of moderate-to-severe psoriasis. (a) Heatmap of differentially expressed genes (DEGs). Unsupervised clustering of lesional (LS) versus non-lesional (NL) DEGs. (b) Scatter plot of the estimated fold change (log2 scale) by real-time reverse transcriptase PCR (RT-PCR, x-axis) and gene array (y-axis) for a selected group of 50 genes (see Table 3). Gray lines outline the two-fold change (FCH) regions. Stars and bullets represent two different low-density cards. Red shows confirmed genes. Classical linear regression analysis (red line) shows a slight compression of FCHs by gene array. Pearson's (r) and Spearman's (ρ) correlation values are presented along with P-values. (c) Venn diagram comparing genes (blue numbers: downregulated genes; red numbers: upregulated genes) identified in this study with those of two published studies employing the same Affymetrix HG U133 Plus 2.0 arrays using the same cutoff criteria (false discovery rate <0.05, FCH>2).

Mentions: We identified 4,175 probe sets as being differentially expressed in psoriasis lesions versus non-lesional matched biopsies when defined by >2-fold change (FCH) and false discovery rate (FDR) <0.05. A heatmap of the DEGs is shown in Figure 1a. The top 50 genes over- or under-expressed in psoriatic lesions are listed in Tables 2a and 2b, respectively. All DEGs are listed in Supplementary Table S2 online. Tables 2a and 2b also specify whether identified genes are regulated in keratinocytes by the cytokines tumor necrosis factor-α (TNF), IL-17, or IFN-γ, which are key mediators of inflammation in psoriasis. The S100A12 gene, a highly inflammatory molecule that binds to the receptor for advanced glycation end products, and is increased in inflammatory dendritic cells and keratinocytes in response to inflammatory cytokines such as IL-17, TNF, and IFN-γ (Nograles et al., 2008; Zaba et al., 2010) exhibited the largest increase in expression.


Expanding the psoriasis disease profile: interrogation of the skin and serum of patients with moderate-to-severe psoriasis.

Suárez-Fariñas M, Li K, Fuentes-Duculan J, Hayden K, Brodmerkel C, Krueger JG - J. Invest. Dermatol. (2012)

The transcriptome of moderate-to-severe psoriasis. (a) Heatmap of differentially expressed genes (DEGs). Unsupervised clustering of lesional (LS) versus non-lesional (NL) DEGs. (b) Scatter plot of the estimated fold change (log2 scale) by real-time reverse transcriptase PCR (RT-PCR, x-axis) and gene array (y-axis) for a selected group of 50 genes (see Table 3). Gray lines outline the two-fold change (FCH) regions. Stars and bullets represent two different low-density cards. Red shows confirmed genes. Classical linear regression analysis (red line) shows a slight compression of FCHs by gene array. Pearson's (r) and Spearman's (ρ) correlation values are presented along with P-values. (c) Venn diagram comparing genes (blue numbers: downregulated genes; red numbers: upregulated genes) identified in this study with those of two published studies employing the same Affymetrix HG U133 Plus 2.0 arrays using the same cutoff criteria (false discovery rate <0.05, FCH>2).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3472561&req=5

fig1: The transcriptome of moderate-to-severe psoriasis. (a) Heatmap of differentially expressed genes (DEGs). Unsupervised clustering of lesional (LS) versus non-lesional (NL) DEGs. (b) Scatter plot of the estimated fold change (log2 scale) by real-time reverse transcriptase PCR (RT-PCR, x-axis) and gene array (y-axis) for a selected group of 50 genes (see Table 3). Gray lines outline the two-fold change (FCH) regions. Stars and bullets represent two different low-density cards. Red shows confirmed genes. Classical linear regression analysis (red line) shows a slight compression of FCHs by gene array. Pearson's (r) and Spearman's (ρ) correlation values are presented along with P-values. (c) Venn diagram comparing genes (blue numbers: downregulated genes; red numbers: upregulated genes) identified in this study with those of two published studies employing the same Affymetrix HG U133 Plus 2.0 arrays using the same cutoff criteria (false discovery rate <0.05, FCH>2).
Mentions: We identified 4,175 probe sets as being differentially expressed in psoriasis lesions versus non-lesional matched biopsies when defined by >2-fold change (FCH) and false discovery rate (FDR) <0.05. A heatmap of the DEGs is shown in Figure 1a. The top 50 genes over- or under-expressed in psoriatic lesions are listed in Tables 2a and 2b, respectively. All DEGs are listed in Supplementary Table S2 online. Tables 2a and 2b also specify whether identified genes are regulated in keratinocytes by the cytokines tumor necrosis factor-α (TNF), IL-17, or IFN-γ, which are key mediators of inflammation in psoriasis. The S100A12 gene, a highly inflammatory molecule that binds to the receptor for advanced glycation end products, and is increased in inflammatory dendritic cells and keratinocytes in response to inflammatory cytokines such as IL-17, TNF, and IFN-γ (Nograles et al., 2008; Zaba et al., 2010) exhibited the largest increase in expression.

Bottom Line: This new analysis identified 4,175 probe sets (representing 2,725 unique known genes) as being differentially expressed in psoriasis lesions compared with matched biopsies of non-lesional skin when the following criteria were applied: >2-fold change and false discovery rate <0.05.These probe sets represent the largest and most comprehensive set of genes defining psoriasis at the molecular level and within the previously unidentified genes, a link to functional pathways associated with metabolic diseases/diabetes and to cardiovascular risk pathways is identified.We identified linkage of functional pathways in lesional skin associated with metabolic diseases/diabetes and cardiovascular risk with those pathways overexpressed in the serum, suggesting a potential linkage between altered gene transcription in the skin and comorbidities commonly seen in patients with moderate-to-severe psoriasis.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Investigative Dermatology, Rockefeller University, New York, New York, USA.

ABSTRACT
Psoriasis is a complex disease with an expanding definition of its pathological features. We sought to expand/refine the psoriasis transcriptome using 85 paired lesional and non-lesional samples from a cohort of patients with moderate-to-severe psoriasis vulgaris who were not receiving active psoriasis therapy. This new analysis identified 4,175 probe sets (representing 2,725 unique known genes) as being differentially expressed in psoriasis lesions compared with matched biopsies of non-lesional skin when the following criteria were applied: >2-fold change and false discovery rate <0.05. These probe sets represent the largest and most comprehensive set of genes defining psoriasis at the molecular level and within the previously unidentified genes, a link to functional pathways associated with metabolic diseases/diabetes and to cardiovascular risk pathways is identified. In addition, we profiled the serum of moderate-to-severe psoriatics compared with healthy controls to assess the overlap of overexpressed lesional genes with overexpressed systemic proteins. We identified linkage of functional pathways in lesional skin associated with metabolic diseases/diabetes and cardiovascular risk with those pathways overexpressed in the serum, suggesting a potential linkage between altered gene transcription in the skin and comorbidities commonly seen in patients with moderate-to-severe psoriasis.

Show MeSH
Related in: MedlinePlus