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Identification of novel keloid biomarkers through profiling of tissue biopsies versus cell cultures in keloid margin specimens compared to adjacent normal skin.

ABSTRACT: OBJECTIVE:Keloid disease (KD) is a benign fibroproliferative skin tumor that results from abnormal wound healing and has no single definitive treatment. This study aims to identify KD biomarkers, which are cellular mediators that can serve as indicators of normal, pathological, and therapeutic processes. METHODS:Bioinformatics analytic approaches, including comprehensive literature searches and DAVID Bioinformatics Resources 2008, were performed on the established KD linkage and previously reported microarray data to identify potential candidate genes for the study. Keloid margins and unaffected skin were obtained from KD patients (n = 4). RNA was extracted from the biopsies and second-passage culture equivalents. Reverse-transcriptase quantitative polymerase chain reactions were used to determine the gene expression levels. Student t tests were used to analyze the statistical significance in differential gene expressions. RESULTS:Nineteen candidate genes were initially selected by bioinformatics analysis. Of the 19 genes, 10 were significantly (P < .05) upregulated in keloid margin biopsy specimens. The top-5 fold changes range from 10-fold to 175-fold, including aggrecan; asporin; inhibin, beta A; tumor necrosis factor-alpha inducible protein 6; and chromosome 5 open reading frame 13. There was no significant differential gene expression between the fibroblasts established using keloid margin or internal control sites. CONCLUSIONS:The transcriptomic data generated from cultures did not consistently correlate to the biopsy equivalents. This study has demonstrated 10 genes that are significantly upregulated in biopsy samples of keloid margin, 5 of which have a fold change higher than 10-fold. Importantly these genes may serve as a potential biomarker for KD.

SUBMITTER: Shih B

PROVIDER: S-EPMC2851107 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature

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Identification of novel keloid biomarkers through profiling of tissue biopsies versus cell cultures in keloid margin specimens compared to adjacent normal skin.

Shih Barbara B McGrouther Duncan Angus DA Bayat Ardeshir A

Eplasty 20100407

<h4>Objective</h4>Keloid disease (KD) is a benign fibroproliferative skin tumor that results from abnormal wound healing and has no single definitive treatment. This study aims to identify KD biomarkers, which are cellular mediators that can serve as indicators of normal, pathological, and therapeutic processes.<h4>Methods</h4>Bioinformatics analytic approaches, including comprehensive literature searches and DAVID Bioinformatics Resources 2008, were performed on the established KD linkage and p ...[more]

PMID: 20418938

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Project description:BackgroundThe objective of this study was to measure skin characteristics in premature (PT), late preterm (LPT), and full-term (FT) neonates compared with adults at two times (T1, T2).MethodsSkin samples of 61 neonates and 34 adults were analyzed for protein biomarkers, natural moisturizing factor (NMF), and biophysical parameters. Infant groups were: <34 weeks (PT), 34-<37 weeks (LPT), and ≥37 weeks (FT).ResultsForty proteins were differentially expressed in FT infant skin, 38 in LPT infant skin, and 12 in PT infant skin compared with adult skin at T1. At T2, 40 proteins were differentially expressed in FT infants, 38 in LPT infants, and 54 in PT infants compared with adults. All proteins were increased at both times, except TMG3, S100A7, and PEBP1, and decreased in PTs at T1. The proteins are involved in filaggrin processing, protease inhibition/enzyme regulation, and antimicrobial function. Eight proteins were decreased in PT skin compared with FT skin at T1. LPT and FT proteins were generally comparable at both times. Total NMF was lower in infants than adults at T1, but higher in infants at T2.ConclusionsNeonates respond to the physiological transitions at birth by upregulating processes that drive the production of lower pH of the skin and water-binding NMF components, prevent protease activity leading to desquamation, and increase the barrier antimicrobial properties.ImpactNeonates respond to the transitions at birth by upregulating processes that drive the production of lower pH of the skin and NMF, prevent protease activity leading to desquamation, and increase the antimicrobial properties of the barrier. The neonatal epidermal barrier exhibits a markedly different array of protein biomarkers both shortly after birth and 2-3 months later, which are differentially expressed versus adults. The major biomarker-functional classes included filaggrin processing, protease inhibitor/enzyme regulators, antimicrobials, keratins, lipids, and cathepsins. The findings will guide improvement of infant skin care practices, particularly for the most premature infants with the ultimate goals mitigating nosocomial infection.

Dataset Information

Identification of novel keloid biomarkers through profiling of tissue biopsies versus cell cultures in keloid margin specimens compared to adjacent normal skin.

Publications

Identification of novel keloid biomarkers through profiling of tissue biopsies versus cell cultures in keloid margin specimens compared to adjacent normal skin.

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