Serum biomarker analysis in patients with recurrent spontaneous abortion

Abstract

Recurrent spontaneous abortion (RSA) occurs in 1–5% of parturients. The sustained therapy and research for RSA is expensive, which is a serious issue faced by both patients and doctors. The aim of the present study was to detect protein expression profiles in the serum of RSA patients and healthy controls, and to identify potential biomarkers for this disease. A 1,000-protein microarray consisting of a combination of Human L-507 and L-493 was used. The microarray data revealed that eight serum protein expression levels were significantly upregulated and 143 proteins were downregulated in RSA patients compared with the healthy controls. ELISA individually validated 5 of these 151 proteins in a larger cohort of patients and control samples, demonstrating a significant decrease in insulin-like growth factor-binding protein-related protein 1 (IFGBP-rp1)/IGFBP-7, Dickkopf-related protein 3 (Dkk3), receptor for advanced glycation end products (RAGE) and angiopoietin-2 levels in patients with RSA. Sensitivity and specificity analyses were calculated by a receiver operating characteristics curve, and were revealed to be 0.881, 0.823, 0.79 and 0.814, with diagnostic cut-off points of 95.44 ng/ml for IFGBP-rp1, 32.84 ng/ml for Dkk3, 147.27 ng/ml for RAGE and 441.40 ng/ml for angiopoietin-2. The present study indicated that these four proteins were downregulated in RSA samples and may be useful as biomarkers for the prediction and diagnosis of RSA. Subsequent studies in larger-scale cohorts are required to further validate the diagnostic value of these markers.

iTRAQ and PRM-based quantitative proteomics in early recurrent spontaneous abortion: biomarkers discovery

“…ITI-H4 and IGFBP have been reported to be associated with miscarriage [12, 13], findings similar to our results. INHBE was identified as a novel putative hepatokine with hepatic gene expression that positively correlated with insulin resistance and body mass index in humans [21].…”

“…Some potential biomarkers for ERSA have been previously reported. Previous studies using LC–MS/MS and ELISA showed a significant decrease in the levels of insulin‑like growth factor‑binding protein‑related protein 1 (IFGBP‑rp1)/IGFBP‑7, Dickkopf‑related protein 3, the receptor for advanced glycation end products (RAGE), and angiopoietin‑2 in patients with RSA [12]. Kim et al [13] used blood samples from healthy and RPL patients to conduct a comparative proteomic study, they performed 2D-PAGE and the selected spots were analyzed with MALDI-TOF/MS.…”

Human chorionic gonadotrophin pharmaceutical formulations of urinary origin display high levels of contaminant proteins–A label‐free quantitation proteomics study

“…Furthermore, IGFPB7 has been recently proposed, by Wu et al. as a biomarker for the prediction and diagnosis of recurrent spontaneous abortion .…”

Implantation and the Fetal Health

“…However, certain maternal characteristics, such as the age and body mass index (BMI), have shown to be very informative, with regard to the predicting miscarriage and stillbirth. The risk of preterm delivery is determined by algorithms that combine these results of the first trimester screening for aneuploidy, increased nuchal translucency, the abnormal ductus venosus flow, and low level of PAPP-A, with the characteristics of the mother [7][8][9]. Such example is the information on the length of the cervical canal from 11-to 13-week gestation [9,10].…”