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

Liu LY, Yang T, Ji J, Wen Q, Morgan AA, Jin B, Chen G, Lyell DJ, Stevenson DK, Ling XB, Butte AJ - BMC Med (2013)

Bottom Line: In 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.Both 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pediatrics, Stanford University, 1265 Welch Road, Room X-163 MS-5415, Stanford, CA 94305, USA. bxling@stanford.edu.

ABSTRACT

Background: Preeclampsia (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.

Methods: Seven 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.

Results: In 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.

Conclusions: Both 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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Related in: MedlinePlus

Expression comparative analyses of PE biomarkers (PE versus controls). Forest plot summarizes the results of placental mRNA expression multiplex analysis, and maternal sera analyte abundance quantification at different early and late gestational age weeks. Line plot represents 95% confidence intervals. PE, preeclampsia.
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Figure 2: Expression comparative analyses of PE biomarkers (PE versus controls). Forest plot summarizes the results of placental mRNA expression multiplex analysis, and maternal sera analyte abundance quantification at different early and late gestational age weeks. Line plot represents 95% confidence intervals. PE, preeclampsia.

Mentions: Forest plots (FigureĀ 2) summarize the PE to control ratios of all 11 validated PE markers across placental expression multiplex analyses, and early and late gestation maternal serum analyses. The biomarkers derived from the proteomic and expression analyses consistently shared the same trend of up- or down-regulation between PE and control samples.


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

Liu LY, Yang T, Ji J, Wen Q, Morgan AA, Jin B, Chen G, Lyell DJ, Stevenson DK, Ling XB, Butte AJ - BMC Med (2013)

Expression comparative analyses of PE biomarkers (PE versus controls). Forest plot summarizes the results of placental mRNA expression multiplex analysis, and maternal sera analyte abundance quantification at different early and late gestational age weeks. Line plot represents 95% confidence intervals. PE, preeclampsia.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4226208&req=5

Figure 2: Expression comparative analyses of PE biomarkers (PE versus controls). Forest plot summarizes the results of placental mRNA expression multiplex analysis, and maternal sera analyte abundance quantification at different early and late gestational age weeks. Line plot represents 95% confidence intervals. PE, preeclampsia.
Mentions: Forest plots (FigureĀ 2) summarize the PE to control ratios of all 11 validated PE markers across placental expression multiplex analyses, and early and late gestation maternal serum analyses. The biomarkers derived from the proteomic and expression analyses consistently shared the same trend of up- or down-regulation between PE and control samples.

Bottom Line: In 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.Both 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pediatrics, Stanford University, 1265 Welch Road, Room X-163 MS-5415, Stanford, CA 94305, USA. bxling@stanford.edu.

ABSTRACT

Background: Preeclampsia (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.

Methods: Seven 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.

Results: In 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.

Conclusions: Both 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.

Show MeSH
Related in: MedlinePlus