Table 1.
Summary of studies using liquid biopsy to diagnose OC.
| Tumor stage | n | Biopsy source | Laboratory method | Genetic marker | AUC (95% CI) | Detection rate, % | Specificity, % (95% CI) | Sensitivity, % (95% CI) | Ref. |
|---|---|---|---|---|---|---|---|---|---|
| cfDNA | |||||||||
| Methylation | |||||||||
| Stage III–IV OC | 30 | Plasma | Microarray | RASSF1A, CALCA, and EP300 | NR | NR | 86.7 (66.7–96.7) | 90.0 (76.7–100) | (22) |
| Stage I–IV OC | 87 (stage I, n = 41; stage II–IV, n = 46) | Serum | Methylation-specific PCR | APC, CDH1, OPCML, RASSF1A, RUNX3, SFRP5, and TFPI2 | Overall: 0.9126 (0.8643–0.9609) Early stage: 0.8916 (0.8258–0.9574) |
NR | 90.57 | 89.66 | (23) |
| Stage I–IV OC | 47 | Plasma | Methylation-specific PCR | RASSF2A | NR | 51.1 | NR | NR | (24) |
| Stage I–IV OC | 43 | Serum | Reduced-representation bisulfite sequencing | COL23A1, C2CD4D, and WNT6 | NR | 57.9 (34.0–78.9) a | 88.1 (77.3–94.3) a | 60.0 (27.4–86.3) a | (25) |
| Stage I–IV OC | 194 | Serum | Methylation-specific PCR | OPCML, TFPI2, and RUNX3 | NR | NR | 90.14 | 91.87 | (26) |
| Stage I–IV (multiple tumors) | 4077 (OC n=65) | Plasma | cfDNA bisulfite conversion and sequencing with ML | Methylation signatures from WGBS | NR | NR | 99.5 (99.0–99.8) | Overall: 51.5 (49.6–53.3) OC: 83.1 |
(27) |
| Chromosomal/structural alterations | |||||||||
| Stage I–IV OC | 32 (16 stage I–II, 16 stage III–IV) | Plasma | Low-coverage WGS | Subchromosomal abnormalities | NR | Overall: 40.6 (23.7–59.4) Early stage: 38 |
93.8 (79.2–99.2) | 40.6 (23.7–59.4) | (28) |
| Stage I–IV OC | 68 (57 with ovarian carcinomas, 11 with benign tumors) | Plasma | Low-coverage WGS | Chromosomal instability | Overall: 0.89 HGSOC: 0.94 |
NR | 91 | 74 | (29) |
| Other | |||||||||
| Stage III–IV OC | 46 | Serum | Tagged-amplicon deep sequencing | NR | NR | NR | 97.5 | 97.5 | (30) |
| ctDNA | |||||||||
| Mutations | |||||||||
| Stage II–III OC | 21 | Serum | NGS | TP53 and BRCA1 | NR | NR | 100.0 | 73.7 | (31) |
| Stage I–IV OC | 96 | Plasma | NGS | 27 cancer-related genes | NR | Stage I: 50 Stage III: 46.2 Stage IV: 83.3 |
NR | Stage I: 43 Stage II: 73 |
(32) |
| Methylation | |||||||||
| Stage I–IV OC | 26 | Serum | Methylation-specific PCR | SFRP1, SOX1, and LMX1A | NR | NR | 75 | 73 | (33) |
| Stage I–IV OC | 33 | Plasma | Microarray | HIC1, PAX5, BRCA1, PGR, and THBS1 | NR | NR | 61.1 | 85.1 | (34) |
| Stage I–IV OC | 106 | Serum | Methylation-specific PCR | RASSF1A | NR | 51 | NR | NR | (35) |
| Stage I–IV OC | 36 | Serum | Methylation-specific PCR | SLIT2 | NR | 80.6 | NR | NR | (36) |
| Stage I–IV OC | 49 | Plasma | Pyrosequencing-based | CDH1 and PAX1 | 0.932 | NR | 56 | 91 | (37) |
| Stage I–IV OC | 70 | Serum | RT-PCR | HOXA9 and HIC1 | 0.95 | NR | 100 | 88.9 | (38) |
| CTCs | |||||||||
| Stage I–IV OC | 129 | Plasma | CAM-based cell enrichment, IHC | EpCAM, CA-125, CD44, separase |
NR | Overall: 88.6 Stage I/II: 41.2 |
95.1 | 83 | (39) |
| Stage I–IV OC | 123 | Plasma | Flow cytometry | NR | NR | 85.3 | 97 | 83 | (40) |
| Stage I–IV OC | 109 | Serum | Immunomagnetic bead screening with multiplex RT-PCR | EpCAM, HER2, MUC1, WT1, P16, PAX8 | NR | Overall: 90 Stage I/II: 93 |
NR | NR | (41) |
| Stage I–IV OC | 30 | Serum | Microfluidic isolation and immunofluorescent staining | CD45, HE4, and epithelial and mesenchymal markers | 0.716 | 73.3 | 63.0 | 73.3 | (42) |
| Stage I–IV OC | 160 | Serum | Immunomagnetic bead screening with multiplex RT-PCR | EpCAM, MUC1, and WT1 | 0.893 | Stage I/II: 74.5 | 92.2 | 79.4 | (43) |
| Stage I–IV OC | 22 | Serum | Microfiltration with morphological and immunofluorescence analyses | EMT markers | NR | 40.9 | NR | NR | (44) |
| Exosomes/exosomal miRNAs | |||||||||
| Stage I–IV OC | 78 | Plasma | Nanoparticle tracking, ELISA | NR | NR | 100 | NR | NR | (45) |
| Stage III–IV OC | 40 | Plasma | LC-MS/MS, nanoparticle tracking, dynamic light scattering, TEM | LPB, FGG, FGA, GSN | GSN: 0.8309 (0.7343–0.9274) FGA: 0.8459 (0.7602–0.9317) FGG: 0.7447 (0.6323–0.8571) LBP: 0.6588 (0.5381–0.7794) |
NR | NR | NR | (46) |
| EOC | 55 | Plasma | smRNA sequencing; RT-PCR | miR-4732-5p | AUC: 0.889 | NR | 85.7 | 82.4 | (47) |
| Circulating miRNAs | |||||||||
| Stage III–IV OC | 168 | Serum | Microarray analysis, RT-PCR | miR-1246 | 0.89 | NR | 77 | 87 | (48) |
AUC, area under the receiver operating characteristic curve; CAM, cell adhesion matrix; cfDNA, cell-free DNA; CI, confidence interval; ctDNA, circulating tumor DNA; CTCs, circulating tumor cells; ELISA, enzyme-linked immunosorbent assay; EMT, epithelial-to-mesenchymal transition;IHC, immunohistochemistry; LC-MS/MS, liquid chromatography with tandem mass spectrometry; NGS, next-generation sequencing; NR, not reported; OC, ovarian cancer; PCR, polymerase chain reaction; RT, reverse transcriptase; smRNA, small messenger RNA; TEM, transmission electron microscopy; WGS, whole-genome sequencing.
a
Within two years of sample collection.