Table 2.
Summary of Extracellular Messenger RNA Biomarkers Evaluated to Differentiate Between Normal Pregnancies and Those with Placental Insufficiency
| Placental insufficiency | Molecular biomarker | Reference |
|---|---|---|
| CRH mRNA | ||
| Onset | ↑ PE | Ng et al. (2003a), Farina et al. (2004a), Purwosunu et al. (2007a), Galbiati et al. (2010) |
| Positive correlation between mRNA levels and the severity of PE | Farina et al. (2004a); Purwosunu et al. (2007a) | |
| ↑ IUGR | Galbiati et al. (2010) | |
| Before onset | ↑ PE (24–36 weeks) | Galbiati et al. (2010) |
| ≅ IUGR (32–36 weeks) | Galbiati et al. (2010) | |
| GCM1 mRNA | ||
| Onset | ↑ PE | Fujito et al. (2006) |
| PLAC1 mRNA | ||
| Onset | ↑ PE | Fujito et al. (2006), Purwosunu et al. (2007a) |
| Positive correlation between mRNA levels and the severity of PE | Purwosunu et al. (2007a) | |
| Before onset | ↑ PE (15–20 weeks) DR for PEP 17.7% at 5% FPR |
Purwosunu et al. (2009) |
| hPL (CSH1) mRNA | ||
| Onset | ≅ PE | Fujito et al. (2006) |
| ↓ PE±IUGR | Farina et al. (2006) | |
| ≅ IUGR | Pang et al. (2009) | |
| GH2 mRNA | ||
| Onset | Positive correlation between mRNA levels and fetal growth (28–41 weeks) | Pang et al. (2009) |
| ≅ IUGR | Pang et al. (2009) | |
| βhCG mRNA | ||
| Onset | ≅ PE | Fujito et al. (2006) |
| PAPP-A mRNA | ||
| Onset | ≅ PE | Fujito et al. (2006), Farina et al. (2006) |
| inhibin A mRNA | ||
| Onset | ↑ PE±IUGR | Farina et al. (2006) |
| selectin P mRNA | ||
| Onset | ↑ PE±IUGR | Farina et al. (2006) |
| ↑ PE | Purwosunu et al. (2007a) | |
| Positive correlation between mRNA levels and the severity of PE | Purwosunu et al. (2007a) | |
| Before onset | ↑ PE (15–20 weeks) DR for PE 24.2% at 5% FPR |
Purwosunu et al. (2009) |
| VEGF mRNA | ||
| Onset | ↑ PE | Purwosunu et al. (2008) |
| Positive correlation between mRNA levels and the severity of PE | Purwosunu et al. (2008) | |
| Before onset | ↑ PE (15–20 weeks) DR for PE 29% at 5% FPR |
Purwosunu et al. (2009) |
| VEGFR-1 (FLT1) mRNA | ||
| Onset | ↑ PE±IUGR | Farina et al. (2006) |
| ↑ PE | Purwosunu et al. (2008) | |
| Positive correlation between mRNA levels and the severity of PE | Purwosunu et al. (2008) | |
| Before onset | ↑ PE (15–20 weeks) the highest DR for PE (58%) at 5% FPR |
Purwosunu et al. (2009) |
| KiSS-1 mRNA | ||
| Onset | ↓ PE±IUGR | Farina et al. (2006) |
| ≅ IUGR | Pang et al. (2009) | |
| PAI-1 (SERPINE1) mRNA | ||
| Onset | ↓ PE±IUGR | Farina et al. (2006) |
| ↑ PE | Purwosunu et al. (2007b) | |
| Positive correlation between mRNA levels and the severity of PE | Purwosunu et al. (2007b) | |
| Before onset | ↑ PE (15–20 weeks) DR for PE 29% at 5% FPR |
Purwosunu et al. (2009) |
| tPA (PLAT) mRNA | ||
| Onset | ↑ PE | Purwosunu et al. (2007b) |
| Positive correlation between mRNA levels and the severity of PE | Purwosunu et al. (2007b) | |
| Before onset | ↑ PE (15–20 weeks) DR for PE 33.9% at 5% FPR |
Purwosunu et al. (2009) |
| Endoglin mRNA | ||
| Onset | ↑ PE | Purwosunu et al. (2008) |
| Positive correlation between mRNA levels and the severity of PE | Purwosunu et al. (2008) | |
| Before onset | ↑ PE (15–20 weeks) detection rate for PE DR 43.5% at 5% FPR |
Purwosunu et al. (2009) |
| ADAM12 mRNA | ||
| Onset | ↑ PE+IUGR | Pang et al. (2009) |
| PTX3 mRNA | ||
| Before onset | ↑ PE (24–36 weeks) | Galbiati et al. (2010) |
| ≅ IUGR (32–36 weeks) | Galbiati et al. (2010) | |
↑ PE, extracellular mRNA levels are increased in patients with PE; ≅ IUGR, extracellular mRNA levels do not differ between controls and patients with IUGR; βhCG, β subunit of human chorionic gonadotropin; GCM1, glial cells-missing 1; CRH, corticotropin-releasing hormone; CSH1, chorionic somatomammotropin hormone 1; GH2, growth hormone 2; hPL, human placental lactogen; mRNA, messenger RNA; PAI-1, plasminogen activator inhibitor type 1; PAPP-A, pregnancy-associated plasma protein-A; PTX3, pentraxin-3; tPA, tissue-type plasminogen activator; VEGFR, vascular endothelial growth factor receptor; DR, detection rate; FPR, false-positive rate; PLAC1, placenta-specific 1.