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A Systems Biology Approach for Studying Heterotopic Ossification： Proteomic Analysis of Clinical Serum and Tissue Samples

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Genomics, Proteomics & Bioinformatics 2018年第3期16卷 212-220页

作者： Erin L. Crowgey Jennifer T. Wyffels Patrick M. Osborn Thomas T. Wood Laura E. Edsberg Nemours Biomedical Research Nemours Alfred I. duPont Hospital for Children Wilmington DE 19803 USA Natural and Health Sciences Researeh Center Center for Wound Healing Research Daemen College Amherst NY 14226 USA Department of Computer and Information Sciences Center for Bioinformatics and Computational Biology University of Delaware Newark DE 19711 USA San Antonio Military Medical Center San Antonio TX 78219 USA

Heterotopic ossification （HO） refers to the abnormal formation of bone in soft tissue. Although some of the underlying processes of HO have been described, there are currently no clinical tests using validated biomarkers for predicting HO formation. As such, the diagnosis is made radiographically after HO has formed. To identify potential and novel biomarkers for HO, we used isobaric tags for relative and absolute quantitation （iTRAQ） and high-throughput antibody arrays to produce a semi-quantitative proteomics survey of serum and tissue from subjects with （HO ＋） and without （HO-） heterotopic ossification. The resulting data were then analyzed using a systems biology approach. We found that serum samples from subjects experiencing traumatic injuries with resulting HO have a different proteomic expression controls. Subsequent quantitative ELISA identified profile compared to those from the matched five blood serum proteins that were differentially regulated between the HO-- and HO- groups. Compared to HO- samples, the amount of insulin-like growth factor I （IGF1） was up-regulated in HO＋ samples, whereas a lower amount of osteopontin （OPN）, myeloperoxidase （MPO）, runt-related transcription factor 2 （RUNX2）,and growth differentiation factor 2 or bone morphogenetic protein 9 （BMP-9） was found in HO ＋ samples （Welch two sample t-test; P 〈 0.05）. These proteins, in combination with potential serum biomarkers previously reported, are key candidates for a serum diagnostic panel that may enable early detection of HO prior to radiographic and clinical manifestations.

关键词： Heterotopic ossification Proteomics runt-related transcriptionfactor 2 Extracellular matrixorganization Keratinization

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