Table 1.
Previously Published Studies Reporting Extracellular miRNA Biomarkers for Prediction or Diagnosis of Pre-eclampsia
| Study and Population Origin | Biofluid | exRNA Isolation Method | exRNA Measurement Method | N; GA Sample Collection | Time Frame | Sensitivity, Specificity, AUC | miRNA PE > Control | miRNA PE < Control |
|---|---|---|---|---|---|---|---|---|
| Yang et al.33 China |
serum | mirVana (Ambion) | small RNA-seq (SOLiD, Applied Biosystems) | 5 (4 pree [2 mild, 2 severe], 1 control) | third trimester, after diagnosis | –,–,– | hsa-miR-521, 520h, 517c-3p, 519d, 520 g, 517b-3p, 542-3p, 136, 518e, 125b, 125a-5p, 519a, 29a, let-7f-3p, 7a-3p | hsa-miR-223, 1260, 320c, 185, 1272, let-7f-5p, 7d-5p |
| Wu et al.31 China (Han) |
plasma | mirVana PARIS (Ambion) | miRNA microarray, 821 miRNAs (Agilent) | 9 (5 severe PE, 4 normal) | 37 and 40 weeks, after diagnosis | –,–,–, p < 0.05, fold-change ≥ 2 | miR-574-5p, 26a,151-3p, 130a, 181a, 130b, 30d, 145, 103, 425, 221, 342-3p, and 24 | miR-144 and 16 |
| Hromadnikova et al.20 Czech Republic | plasma | mirVana (Ambion) | qRT-PCR, 7 C19MC miRNAs | 168 (24 mild PE, 39 severe PE, 27 FGR, 23 ghtn, 55 normal) | after diagnosis | –,–,– | hsa-miR-516-5p, 517-5p, 520-5p, 525-5p, 526a | |
| Li et al.22 China |
plasma | mirVanaTM miRNA Isolation Kit (Ambion) | discovery: small RNA-seq (SOLiD, Applied Biosystems) validation: qRT-PCR | discovery: 4 mild PE, 4 severe PE, 4 normal. validation: 16 mild PE, 22 severe PE, 32 normal. | 34–37 weeks, after diagnosis | –,–,– | miR-141 and miR-29a (mild PE versus control) | miR-144 (mild PE and severe PE versus control) |
| Luque et al.23 Barcelona |
serum | miRNeasy Mini kit (QIAGEN) | TaqMan OpenArray Human MicroRNA Panel, 754 miRNAs, (Applied Biosystems) | 31 PE, 44 normal | 11–136 weeks, asymptomatic | –,–,– | miRNAs: miR-192, 143, and -125b | miR-127, -942, -126∗, and -221, did not validate |
| Xu et al.32 China |
placenta and plasma | not given | placenta: mammalian miRNA chip array, 435 human miRNAs (V2.0, Capitalbio). Plasma: TaqMan qPCR. | 53 (20 severe PE, 33 normal) | 15–18 and 35–38 weeks, asymptomatic | –,–,– | miR-210 | miR-18a, miR-19b1, and miR-92a1 |
| Stubert et al.28 Germany |
serum | QIAamp Circulating Nucleic Acid Kit (QIAGEN) | TaqMan Low Density Array Human MicroRNA Card Set v3.0, 754 miRNAs (Applied Biosystems) | 26 (13 HELLP, 13 controls) | 28–41 weeks, at diagnosis | miR-122e: AUC = 0.82 | miR-122, miR-758, and miR-133a (>2-fold) | miR-573, miR-766, and miR-409-3p |
| Ura et al.30 Italy |
sera | mirVana PARIS with 2× acid-phenol/chloroform extraction | TaqMan Low Density Array Human MicroRNA Card Set v3.0, 754 miRNAs (Applied Biosystems) | 48 (24 severe PE, 24 control) | 12–14 weeks, asymptomatic | validated miR-1233, miR-520a, miR-210, miR-14 | miR-1233; miR-650; miR-520a; miR-215; miR-210; miR-25; miR-518b; miR-193a-3p; miR-32; miR-204; miR-296-5p; miR-15 | miR-126; miR-335; miR-144; miR-204; miR-668; miR-376a; miR-15b |
| Yang et al.34 China |
plasma and placenta | TRIzol | small RNA-seq (SOLiD, Applied Biosystems) | 5 (2 mild PE, 2 severe PE, 1 control) | 244–283 days, at diagnosis (plasma) and delivery (placenta) | –,–,– | miR-126, miR-126∗, miR-130a, miR-135b, miR-142-3p, miR-149, miR-188-5p, miR-18a, miR-18b, miR-203, miR-205, miR-224, miR-27a, miR-29a, miR-301a, miR-517c, miR-518-3p, miR-518e, miR-519d and miR-93 | |
| Miura et al.25 Japan | plasma | mirVana (Ambion) | qRT-PCR of 10 C19MC miRNAs | 40 (20 cases [severe]: 20 controls) | 27–34 weeks, after diagnosis | –,–,– | hsa-miR-518b, 1323, 516b, 516a-5p, 525-5p, 515-5p, 520h, 520a-5p, 519d, 526b | |
| Jairajpuri et al.21 Bahrain |
plasma | miRNeasy (QIAGEN) | custom miScript miRNA PCR array, 84 miRNAs (QIAGEN) | 22 (15 cases [7 mild, 8 severe]: 7 controls) | third trimester, at delivery | –,–,– | hsa-miR- 215, 155, 650, 210, 21, 518b, 29a | hsa-miR-15b, 144, 18a, 19b1 |
| Yoffe et al.35 UK |
plasma | miRNeasy (QIAGEN) | small RNA-seq (TruSeq, Illumina) | 75 (35 cases [early onset]: 40 controls) | pre-symptomatic, 11 weeks 0 days to 13 weeks 6 days | 0.72, 0.8, 0.86 | hsa-miR-4433b, 221, hsa-let-7g | hsa-miR-182, 10b, 25, 99b, 143, 151a, 191, 146b, 486 |
| Salomon et al.27 Chile |
plasma | miRNeasy Mini Kit (QIAGEN) from exosomes isolated by density gradient ultracentrifugation | small RNA-seq (TruSeq, Illumina) | 47 (15 PE, 32 control) | 11–14 weeks, 22–24 weeks, 32–36 weeks | –,–,–, p < 0.05 | hsa-miR-486-5p, 423-5p, 451a, 107, 15a-5p, 335-5p, 92a-3p, 103a-3p | hsa-miR-126-3p |
| Gunel et al.18 Turkey | plasma, placenta | mirVana miRNA Isolation kit (Ambion) plasma | G4870A SurePrint G3 Human v16 miRNA 8 × 60 K Microarray, 1368 miRNAs (Agilent) | 36 (18 severe PE at 32 and 34 weeks, 18 control at 37 and 40 weeks) | 32–40 weeks, at delivery and diagnosis | –,–,– | hsa-miR-877∗, hsa-miR-118 | hsa-miR-1539, hsa-let-7b∗, hsa-miR-191∗, hsa-miR-23c, hsa-miR-33b∗, hsa-miR-425∗, hsa-miR-4313, hsa-miR-550a, hsa-miR-933, hsa-miR-7f-1∗ |
| Gan et al.17 China | plasma, urine cells | Trizol LS reagent (Invitrogen) | qRT-PCR, miR-210, miR-155, miR-125b-5p, miR-125a-5p | 40 (20 PE, 20 control) | 20–34 weeks, at diagnosis | miR-210: AUC = 0.750; miR-155: AUC = 0.703 | miR-210 and miR-155 in plasma | |
| Timofeeva et al.29 Russia |
plasma | miRNeasy (QIAGEN) | small RNA-seq (NEBNext, NEB) on 12 cases from cohort 1; qRT-PCR on cohort 2 | cohort 1– 54 (28 cases [16 early onset, 12 late onset]: 26 controls [10 < 34 weeks, 16 > 37 weeks]); at delivery. cohort 2–16 (6 cases: 10 controls); 11–13, 24–26, 30–32 weeks. | hsa-miR-423-5p: Sensitivity = 0.875; Specificity = 0.80; AUC = 0.844 | hsa-miR-423-5p, 519a-3p, 629-5p, hsa-let-7c-5p cohort 1; hsa-miR-423-5p cohort 2 at 11–13 weeks | ||
| Hromadnikova et al.19 Czech Republic | plasma | mirVana (Ambion) | qRT-PCR of 6 C19MC miRNAs | 97 (39 cases [21 pre-eclampsia, 18 IUGR]: 58 controls) | 10–13 weeks | hsa-miR-517-5p: Sensitivity = 0.429; Specificity = 0.862;p < 0.05 | hsa-miR-517-5p, 518b, 520h | |
| Martinez-Fierro et al.24 Mexico | serum | miRNeasy Mini Kit (QIAGEN | TaqMan Low Density Array Human MicroRNA Card Set v2.0, focused on 51 C19MC miRNAs (Applied Biosystems) | 34 (16 PE, 18 control) | 12, 16, and/or 20 weeks, asymptomatic, longitudinal | –,–,–, p < 0.05 | hsa-miR-520c-3p (16 weeks); hsa-miR-512-3p, 518f-3p, 520d-3p (20 weeks) | |
| Motawi et al.26 Egypt |
plasma | miRNeasy Mini Kit (QIAGEN) from exosomes isolated by ultracentrifugation | TaqMan miRNA qPCR of hsa-miR-136, 494, and 495 | 200 (100 PE [23 < 20 weeks, 77 > 20 weeks], 100 control [20 < 20 weeks], 80 > 20 weeks) | at diagnosis | <20 weeks: hsa-miR-136 0.95, 1.00, 1.000; hsa-miR-494 0.86, 0.95, 0.868; hsa-miR-495 0.90, 0.83, 0.940, p < 0.05 | <20 weeks and >20 weeks: hsa-miR-136, 494 and 495 |