• Bmc Med · Nov 2013

    Integrating multiple 'omics' analyses identifies serological protein biomarkers for preeclampsia.

    • Linda Y Liu, Ting Yang, Jun Ji, Qiaojun Wen, Alexander A Morgan, Bo Jin, Gongxing Chen, Deirdre J Lyell, David K Stevenson, Xuefeng B Ling, and Atul J Butte.
    • Department of Pediatrics, Stanford University, 1265 Welch Road, Room X-163 MS-5415, Stanford, CA 94305, USA. bxling@stanford.edu.
    • Bmc Med. 2013 Nov 6; 11: 236.

    BackgroundPreeclampsia (PE) is a pregnancy-related vascular disorder which is the leading cause of maternal morbidity and mortality. We sought to identify novel serological protein markers to diagnose PE with a multi-'omics' based discovery approach.MethodsSeven previous placental expression studies were combined for a multiplex analysis, and in parallel, two-dimensional gel electrophoresis was performed to compare serum proteomes in PE and control subjects. The combined biomarker candidates were validated with available ELISA assays using gestational age-matched PE (n=32) and control (n=32) samples. With the validated biomarkers, a genetic algorithm was then used to construct and optimize biomarker panels in PE assessment.ResultsIn addition to the previously identified biomarkers, the angiogenic and antiangiogenic factors (soluble fms-like tyrosine kinase (sFlt-1) and placental growth factor (PIGF)), we found 3 up-regulated and 6 down-regulated biomakers in PE sera. Two optimal biomarker panels were developed for early and late onset PE assessment, respectively.ConclusionsBoth early and late onset PE diagnostic panels, constructed with our PE biomarkers, were superior over sFlt-1/PIGF ratio in PE discrimination. The functional significance of these PE biomarkers and their associated pathways were analyzed which may provide new insights into the pathogenesis of PE.

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