Early pregnancy protein multiplex screening reflects circulating and urinary divergences associated with the development of preeclampsia

ABSTRACT

Background: Preeclampsia, a pregnancy disorder characterized by hypertension and proteinuria, represents the leading cause of fetal and maternal morbidity and mortality in developing countries. The identification of novel and accurate biomarkers that are predictive of preeclampsia is necessary to improve the prognosis of patients with preeclampsia.

Objective: To evaluate the preeclampsia predictive value of 34 angiogenic-related proteins.

Methods: We performed a nested cohort case-control study of pregnant women. The profile of the 34 proteins was evaluated at 12, 16, and 20 gestational weeks (GWs), using urine/plasma from 16 women who developed preeclampsia and 20 normotensive pregnant controls by Bio-Plex Pro^TM Human Cancer Biomarker Panels 1 and 2.

Results: The urine concentration of soluble epidermal growth factor receptor (sEGFR), hepatocyte growth factor (HGF), angiopoietin-2 (ANG-2), endoglin (ENG), soluble fas ligand (sFASL), interleukin 6 (IL-6), placental growth factor (PLGF), and vascular endothelial growth factor A (VEGF-A) at 12 GW, prolactin (PRL), ANG-2, transforming growth factor alpha (TGF-α), and VEGF-A at 16 GW, and soluble IL-6 receptor alpha (sIL-6Rα), ANG-2 and sFASL at 20 GW, were different between groups (p < 0.05). The concentration cut-off values calculated in this study for the mentioned proteins, predicted an increased risk to developing preeclampsia in a range of 3.8–29.8 times in the study population.

Conclusion: The proteins sEGFR, HGF, ANG-2, sFASL, IL-6, PLGF, VEGF-A, PRL, TGF-α FGF-b, sHER2/Neu sIL-6Rα, ENG, uPA, and insulin-like growth factor binding protein 1 (IGFBP-1), were predictive of the development of preeclampsia and their use as markers for this disease should be considered.

KEYWORDS:

• Angiogenesis
• biomarkers
• cancer
• placenta
• preeclampsia
• screening
• urine

Acknowledgments

Authors thank all the study participants. We are grateful to the clinical staff of the Centro de Salud Urbano “José Castro Villagrana” and from the Hospital de la Mujer Zacatecana for their invaluable assistance in obtaining samples. We also gratefully acknowledge the support of Dr. Raymundo Orozco-Covarrubias, Dr. José Luis Durán-Aguayo, Dr. Martín Cardona-Domínguez, Dr. Rosbel Castro, and Dr. Raúl Hernández-León (SSZ) in patient enrollment

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Supplemental data

Supplemental data for this article can be accessed here.

Additional information

Funding

This work was funded by the following CONACYT Grants: -SEP-CB-2009-01-0128567, -FOMIX M0024-2013-01-203220, -SALUD-2010-138721, -SALUD-2012-01-181124, -INFR-254106 and 225520. The manuscript edition costs were covered in part with PFC support (to CA-UAZ-207).

Notes on contributors

Margarita L Martinez-Fierro

MLMF, YOC, MACB, AGA, participated in the design of the study and in the coordination of patient recruitment. IGV, RMCH, MECL, and CCDR carried out the samples processing and the performance of Bioplex assays. MLMF, CCDR, IDE, ECV, EISH, RCM, JMOR, LOSS, and MECL, participated in data acquisition, analysis and interpretation. MLMF, CCDR, MEJ, RMCH, and IGV were involved in the preparation of manuscript. MLMF conceived the study, participated in its design and coordination, performed the statistical analysis, and drafted the manuscript. All authors read and approved the final manuscript.