Table 3.
Summary of studies using liquid biopsy to predict outcomes in patients with ovarian cancer.
| Tumor subtype and stage | n | Specimen | Laboratory method | Genetic marker | Setting | Outcome prediction | Ref. |
|---|---|---|---|---|---|---|---|
| ctDNA or cfDNA | |||||||
| Mutations | |||||||
| Stage I–IV OC | 10 | Serum | ddPCR | Tumor-specific | Relapsed disease | Poor OS (P = 0.0194) and PFS (P = 0.0011) | (70) |
| Stage I–IV OC | 11 | Plasma | ddPCR | Tumor-specific | After debulking surgery | Early recurrence detection; tumor volume following recurrence | (116) |
| Stage I–IV EOC | 137 | Plasma | DNA sequencing, PCR | TP53 | NR | Poor OS (P = 0.02) | (89) |
| Relapsed HGSOC | 40 | Plasma | Microfluidic digital PCR | TP53 | Chemotherapy | TTP (HR: 0.22 [95% CI, 0.07–0.67], P = 0.008) | (90) |
| Stage II–IV HGSOC | 102 | Plasma | ddPCR | TP53 | PBC | TTP (P = 0.038) | (92) |
| HGSOC | 97 | Plasma | NGS | BRCA1/BRCA2 reversion | PARP inhibitor (rucaparib) | Poor PFS (HR: 8.33, P < 0.0001) | (96) |
| Methylation | |||||||
| Stage I–IV HGSOC | 59 | Plasma | Methylation-sensitive high-resolution melting analysis | RASSF1A promoter | Platinum-based chemotherapy | Poor OS (HR: 2.76 [95% CI, 1.102–6.915], P = 0.030) | (117) |
| Platinum-resistant BRCA-mutated ovarian cancer | 32 | Plasma | Methylation-specific ddPCR | HOXA9 promoter | Treatment with PARP inhibitor (veliparib) | Poor OS (P < 0.002) and PFS (P < 0.0001) | (100) |
| Stage I–IV recurrent ovarian cancer | 100 | Plasma | Methylation-specific ddPCR | HOXA9 promoter | Chemotherapy followed by maintenance therapy with PARP inhibitors or bevacizumab | Poor OS (HR: 2.17 [1.18–3.98]; P = 0.013) | (101) |
| Other | |||||||
| Stage I–IV OC | 164 | Plasma | RT-PCR | cfDNA ≥ 22,000 IU/mL | Before surgery | Poor DFS (multivariate HR, 2.22 [1.16–4.21]; P = 0.01) | (118) |
| Stage I–IV EOC | 36 | Serum | RT-PCR | RAB25 downregulation | Before surgery | Poor OS (HR: 33.6 [95% CI, 1.8–634.8], P = 0.02) and DFS (HR: 18.2 [95% CI, 2.0–170.0], P = 0.01) | (119) |
| Stage I–IV EOC | 63 | Serum | PCR-based fluorescence microsatellite analysis | LOH at 6q and 10q | Before surgery and after chemotherapy | OS (P = 0.030) | (120) |
| CTCs | |||||||
| Stage I–IV EOC | 90 | Peripheral blood | Immunomagnetic assay | MOC-31+ CTCs | Prior to adjuvant chemotherapy | No association with prognosis | (121) |
| Stage I–IV EOC | 64 | Peripheral blood | Immunocytochemistry | NR | Prior to debulking surgery | No association with prognosis | (122) |
| Stage I–IV EOC | 71 | Peripheral blood | Immunomagnetic CTC enrichment | Cell adhesion matrix molecules and epithelial markers | NR | Poor disease-free survival (P = 0.042) | (123) |
| Stage I–IV EOC | 122 | Peripheral blood | Immunomagnetic enrichment | EpCAM, MUC-1, HER-2 | At primary diagnosis and/or after platinum-based chemotherapy | Poor OS before surgery (P = 0.0054) and after chemotherapy (P = 0.047) | (124) |
| Stage I–IV EOC | 216 | Peripheral blood | CTC enrichment | EpCAM+, cytokeratin+, CD45− | Platinum-based chemotherapy | Poor PFS (HR: 1.58 [95% CI, 0.99–2.53], P = 0.0576) and OS (HR: 1.54 [95% CI, 0.93–2.54], P = 0.0962) | (55) |
| Stage I–IV EOC | 129 | Plasma | CAM-based cell enrichment, IHC | EpCAM, CA-125, DPP4, CD44, seprase and cytokeratins | Before surgery | Poor OS (P = 0.0219) and PFS (P = 0.0024) | (39) |
| Stage I–IV EOC | 143 | Plasma | Immunomagnetic CTC enrichment, multiplex RT-PCR | ERCC1+ CTCs | Platinum-based chemotherapy | Poor OS (HR: 2.5 [95% CI, 1.1–5.5], P = 0.026) and PFS (HR: 3.4 [95% CI, 1.4–8.3], P = 0.009) | (104) |
| Stage I–IV EOC | 123 | Plasma | iCTC flow cytometry assay | Seprase and CD44 | Before chemotherapy | Associated with relapse during and after treatment | (40) |
| Stage I-IV ovarian cancer | 65 | Plasma | AdnaTest Ovarian Cancer, multiplex RT-PCR | ERCC1 | Platinum-based chemotherapy | Poor OS (P = 0.0008) and PFS (P = 0.0293) | (105) |
| Stage I–IV ovarian cancer | 54 | Serum | Nanoroughened microfluidic-based enrichment | EpCAM+, DAPI+, CD45– | Platinum-based chemotherapy | Poor PFS (HR: 1.3 [95% CI, 0.230–7.145], P = 0.035) | (106) |
| Stage I–IV ovarian cancer | 266 | Plasma | Density gradient centrifugation, immunostaining | EpCAM, EGFR, HER2, MUC1, cytokeratins, CD45 | Samples collected at diagnosis and after first-line adjuvant first-line chemotherapy | Baseline CTC numbers associated with poor OS (HR: 3.305 [95% CI, 1.386–7.880], P = 0.007) and PFS (HR: 5.671 [95% CI, 1.560–20.618], P = 0.008) | (125) |
| Stage I–IV EOC | 109 | Serum | Immunomagnetic bead screening, RT-PCR | EpCAM+ CTCs, HER2+ CTCs | Platinum-based chemotherapy | Association with tumor stage (P = 0.034), | (41) |
| Stage III–IV HGSOV | 46 | Plasma | Shallow whole-genome sequencing | 19p31.11 and 19q13.42 amplification | During platinum-based chemotherapy | Poor PFS (HR: 3.31 [95% CI, 1.33–9.13]; P = 0.011) | (126) |
| Stage I–IV ovarian cancer | 1285 | NR | Different enrichment methods | NR | Chemotherapy or surgery | Poor OS (HR: 1.77 [95% CI, 1.42–2.21], P < 0.00001) and PFS (HR: 1.53 [95% CI,1.26–1.86], P < 0.0001) | (127) |
| Stage I–IV EOC | 160 | Serum | Immunomagnetic bead screening combined with multiplex RT-PCR | EpCAM, MUC1, and WT1 | Platinum-based chemotherapy | Poor OS (HR: 1.900 [95% CI, 1.020−3.540]; P = 0.043) | (43) |
| Exosomes | |||||||
| Stage I–IV EOC | 78 | Plasma | Nanoparticle tracking analysis, ELISA | Exosomal HLA-G | Platinum-based chemotherapy | Poor PFS (HR: 1.8 [95% CI, 1.1–3.6]; P = 0.029) | (45) |
| Stage III–IV EOC | 40 | Plasma | Liquid chromatography-tandem mass spectrometry, nanoparticle tracking analysis, dynamic light scattering, transmission electron microscopy | LPB, FGG, FGA, GSN | NR | Poor OS and PFS | (46) |
| Circulating miRNAs | |||||||
| Stage I–IV EOC | 70 | Serum | RT-PCR | miR-200a, miR-200b, miR-200c | NR | Expression levels of miR-200a and miR-200c were associated with disease progression (P = 0.04 and P < 0.001) | (128) |
| Stage I–IV EOC | 207 | Serum | TaqMan Low-Density Arrays, RT-PCR | miR-1274B, miR-200b, miR-141 | Before treatment with bevacizumab plus chemotherapy | Low levels of miRNAs are associated with improved OS mir 1274B: HR = 0.846 (95% CI, 0.70–1.02); P = 0.085 miR 200b: HR = 0.798 (95% CI, 0.68–0.94); P = 0.006 miR-141: HR = 0.914 (95% CI, 0 0.81–1.03); P = 0.153 |
(129) |
cfDNA, cell-free DNA; CI, confidence interval; ctDNA, circulating tumor DNA; CTCs, circulating tumor cells; ddPCR, droplet digital PCR; EMT, epithelial-to-mesenchymal transition; EOC, epithelial ovarian carcinoma; HGSOC, high-grade serous ovarian cancer; HR, hazard ratio; IHC, immunohistochemistry; NGS, next-generation sequencing; NR, not reported; LOH, loss of heterozygosity; OS, overall survival; PCR, polymerase chain reaction; PFS, progression-free survival; RT-PCR, reverse-transcriptase PCR; TTP, time to progression.