Electrophoresis 2013, 34, 493–500 493 Mi-Ryung Park 1 Jong-Yi Park 1 Deug-Nam Kwon 1 Ssang-Goo Cho 1 Chankyu Park 1 Han-Geuk Seo 1 Yeoung-Gyu Ko 2 Sangiliyandi Gurunathan 1 Jin-Hoi Kim 1 1 Department of Animal Biotechnology, Konkuk University, Seoul, Republic of Korea 2 Animal Genetic Resources Station, National Institute of Animal Science, RDA, Namwon, Republic of Korea Received April 4, 2012 Revised October 9, 2012 Accepted October 11, 2012 Research Article Altered protein profiles in human umbilical cords with preterm and full-term delivery Several biomarkers are routinely used clinically for predicting preterm labor; however, these factors are either nonspecific or detected too late. Here, we performed protein pro- files in preterm- and term-derived human umbilical cord by using 2DE. Approximately 200 different proteins were identified between preterm- and term-delivered umbilical cords. Among them, 48 proteins were identified. A comparison of preterm proteome to that of term proteome revealed potential candidates for biomarkers, such as hypoxia-inducible proteins, phosphorylated heat-shock protein 27 (HSP27), transgelin, vimentin, and trans- ferrin that are specific to preterm umbilical cords. Especially, HSP27 in preterm-derived umbilical cords shows a significant increase in the mono- and tetra-phosphorylation. The real importance of all of HSP27 phosphorylation as well as hypoxia-inducible factor 1alpha, and glyceraldehyde 3-phosphate dehydrogenase require further validation in vitro and in vivo; nevertheless, we believe that they could represent promising diagnostic targets for detection of sudden early delivery. In conclusion, the results of the current study may provide important insights into the molecular mechanisms underlying umbilical cord development. Keywords: Heat-shock protein 27 / Human umbilical cord / Hypoxia / Preterm / Proteomics DOI 10.1002/elps.201200197 1 Introduction Adverse pregnancy outcomes such as preeclampsia, small for gestational age infants, preterm delivery, and placental abruption are associated with higher mortality [1–3]. Among them, preterm birth is defined by the World Health Organi- zation (WHO) as birth prior to 37 completed weeks of ges- tation [4] and continues to provide an enormous challenge in the delivery of perinatal health care, estimated to affect approximately 13 million births annually worldwide [5, 6]. Many factors have been implicated, including an increase in maternal age and use of assisted reproductive techniques, which resulted in increases in the risk of multiple preg- nancy [7–9], increasing maternal body mass index and the influence of obesity [10] continued maternal smoking during pregnancy and infection [11, 12]. A number of human umbil- Correspondence: Dr. Jin-Hoi Kim, Department of Animal Biotech- nology, Konkuk University, Seoul 143-701, Republic of Korea E-mail: jhkim541@konkuk.ac.kr Fax: +82-2-458-5414 Abbreviations: DBP, vitamin D-binding protein precur- sor; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; GRP78, 78 kDa glucose-regulated protein precursor; HIF-1, hypoxia-inducible factor 1alpha; HSP27, heat-shock protein 27; HUVEC, human umbilical vein-derived endothelial cells; LDH, lactate dehydrogenase; p38, mitogen-activated protein kinases 14; Prx, peroxiredoxin ical cord malformations have been reported, most of which involve blood vessels [13]. However, the proteome of human umbilical cords has not described yet, and there is very lit- tle known about umbilical cord protein profiles. In order to identify the pathological processes involved in placental in- sufficiency, it is important to characterize the normal protein profile during homeostasis in healthy umbilical cord tissue. Recent advances in genomic and proteomic profiling tech- nology have made it possible to apply computational meth- ods to detect changes in protein profiles and their association to disease conditions, thereby hastening the identification of potential candidates for biomarkers that may contribute to multimarker combinations with better diagnostic perfor- mance. New biomarkers that could be used individually or in combination with an existing modality for cost-effective screening of any diseases are still urgently needed. Discover- ing disease-associated biomarkers was carried out by using a classical approach such as 2D-PAGE. Jungblut et al. [14] pre- sented a critical view on the terminology in proteomics and defined the protein species chemically as the smallest unit, which can be correlated to a function. Recently, Schl ¨ uter et al. [15] proposed a systematic nomenclature for the comprehen- sive description of protein species. To identify critical proteins that differentially regulated during preterm and full-term de- livery, we have employed proteomic approach. This method is capable of quantitatively mapping the total proteome and has proven very useful studies of complex processes. Colour Online: See the article online to view Fig. 1 in colour. C  2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.electrophoresis-journal.com