Reproducible Novel Transcriptional Differences Between Psoriatic Lesional and Non-Lesional Skin Show Increased Inflammation and Metabolism

August 2015 | Volume 14 | Issue 8 | Original Article | 794 | Copyright © 2015

Daniel J. Aires MD JD,a Graham Rockwell PhD,b Alan Menter MD,c Colton Nielson,d Jo Wick PhD,e Stephanie Sedivy MD,f Ossamma Tawfik MD PhD,g Anne Bowcock PhD,h and Animesh A. Sinha MD PhDi

aDivision of Dermatology, University of Kansas Medical Center, Kansas City, KS
bDepartment of Bioinformatics, Boston University, Boston, MA
cDept. of Dermatology, Baylor University Medical Center, Dallas, TX
dUniversity of Kansas School of Medicine, Kansas City, KS
eDepartment of Biostatistics, University of Kansas Medical Center, Kansas City, KS
fDermatopathology, Physician’s Reference Laboratory, Overland Park, KS
gDepartment of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS
hDivision of Human Genetics, Washington University, St. Louis, MO
iDepartment of Dermatology, University at Buffalo, Buffalo, NY

Abstract

BACKGROUND: Psoriasis is a common but complex chronic inflammatory skin Disease. Array-based studies can help identify therapeutic targets.
OBJECTIVE: To reproducibly assess single-gene transcriptional changes in psoriatic skin.
METHODS: We evaluated 210 top candidate genes from a first psoriasis study group (population 1), and then confirmed differential expression in a second independent psoriasis study group (population 2).
RESULTS: One hundred and thirty-eight differentially expressed genes were replicated in the 2 studies, of which 57 have not previously been reported as associated with psoriasis. This is significantly greater than the 10 expected false positives. Lesional skin vs uninvolved areas showed inflammatory and cell regulation changes.
CONCLUSION: Previously undescribed psoriasis-associated genes revealed in this study may provide potential future targets for development and assessment of novel therapeutic agents for psoriasis.

J Drugs Dermatol. 2015;14(8):794-800.

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INTRODUCTION

Psoriasis (PS) is a common but complex chronic inflammatory skin disease. It is characterized by red, scaly plaques, which commonly present on the extensor surfaces of the body. Psoriasis affects approximately 2% to 3% of the world’s population.1,2 Its prevalence varies among different populations depending greatly upon climate, environmental antigen exposure, and genetic susceptibility. Studies suggest overlap of susceptibility loci between psoriasis and other autoimmune processes. Treatment may be both morbid and expensive.3 Reliable single-gene transcriptional changes in psoriatic skin can potentially identify future therapeutic targets for the treatment of psoriasis.4

Microarray-based studies can provide insights into the pathogenesis of psoriasis.5 Krueger et al successfully compared differently-derived psoriasis data sets using gene set enrichment analysis (GSEA).6 GSEA uses complex algorithms to identify multi-gene pathways that share common biological function, chromosomal location, or regulation, rather than individual genes.7,8 Bigler et al showed that gene expression changes in psoriatrc lesions can be consistent across different studies, despite differences in patient selection, sample handling, and microarray platforms.9 The present study used a 2-step single-gene analysis to compare similarly- derived but not identical psoriasis data sets. The goal was to reproducibly identify differently-expressed single genes that could provide new genetic targets for future functional studies and therapy development for psoriasis.

MATERIALS AND METHODS

To obtain data for Set 1, a sample of red scaly “lesional” skin and a sample of normal appearing “non-lesional” skin were obtained by punch technique from each of 15 psoriasis patients. Diagnosis of psoriasis was confirmed by clinical evaluation and histology. Additional samples of normal appearing non-lesional skin were obtained from 6 normal controls who were disease

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