Computational Analysis of Six Expression Studies Reveals miRNA-mRNA Interactions and 25 Consistently Disrupted Genes in Atopic Dermatitis

Atopic dermatitis (AD), known as eczema, affects millions of people worldwide and is a chronic inflammatory skin disease. It is associated with risks of developing asthma, food allergies, and various other diseases related to the immune system. AD can also negatively affect the self-esteem of patients. Gene expression data could yield new insights into molecular mechanisms and pathways of AD, however, results often vary drastically between studies. In this study, expression data from five mRNA studies and one miRNA study were combined to identify differences between atopic dermatitis skin and unaffected, normal skin. Protein interaction network analysis and Panther analysis revealed that pathways related to leukocyte behavior, antimicrobial defense, metal sequestration, and type 1 interferon signaling were significantly affected in AD. In total, 25 genes, such as SERPINB4 and ST1007 were consistently identified to be disrupted across studies. Within the 25, 11 were underexpressed and 14 were overexpressed. Several genes implicated in skin cancers were among the 25. We also identified underexpressed 13 miRNAs, many of which regulate some of the 14 overexpressed genes. Gene FOXM1 was targeted by 6 underexpressed miRNAs and was on average overexpressed by 9.53 times in AD. Presumably, underexpression of miRNAs led to overexpression of their gene targets. The results of this research have implications for diagnostic tests and therapies for AD. It elucidates molecular mechanisms of AD with greater confidence than does a single study alone. Future steps include experiments regarding the role of SERPINB4, ST1007, neutrophil and leukocyte aggregation, and interferon signaling in AD. Additionally, the associations between AD and skin cancers should be further investigated. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study did not receive any funding. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: All data used in this study were retrieved from the public database, Gene Expression Omnibus. They are publicly available at the links below. GSE32924: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE32924 GSE6012: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE6012 GSE36842: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE36842 GSE16161: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE16161 GSE5667: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE5667 GSE31408: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE31408 I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data used in this study were retrieved from the public database, Gene Expression Omnibus. They are publicly available at the links below. GSE32924: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE32924 GSE6012: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE6012 GSE36842: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE36842 GSE16161: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE16161 GSE5667: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE5667 GSE31408: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE31408