Table 2.
Studies on ctDNA, DNA, CTC and microRNA in ovarian cancer.
| Author (Year), References | Number of OC Patients | Specimen | Method | Genetic Marker/Antigen | Detection Rate (%) | Detection Rate (%) (I-II Stage) | Sensitivity (%) | Specificity (%) |
|---|---|---|---|---|---|---|---|---|
| K.K Lin et al. (2019) [33] | 112 germline or somatic BRCA-mutant HGOC | Plasma (ctDNA) | Targeted-NGS | BRCA1, BRCA2, TP53 | 96 for TP53 | NR | NR | NR |
| Y. Wang et al. (2018) [34] | 83 OC | Plasma (ctDNA) | Pap SEEK-PCR-based error-reduction technology Safe-SeqS | 18 genes + assay for aneuploidy | 43 | 35 | NR | 100 |
| Y. Wang et al. (2018) [34] | 83 OC | Plasma (ctDNA) + Pap Brush samples | Pap SEEK-PCR-based error-reduction technology Safe-SeqS | 18 genes + assay for aneuploidy | 63 | 54 | NR | 100 |
| P.A. Cohen et al. (2018) [35] | 54 OC | Plasma (ctDNA) + proteins | CancerSEEK Targeted NGS |
16 gene panel + 41 protein biomarkers | 98 | 38 | NR | >99 AUC = 0.91 |
| J. Phallen et al. (2017) [36] | 42 OC | Plasma (ctDNA) | Targeted NGS (TEC-Seq) and ddPCR | 55 gene panel | 71 | 68 | NR | 100 |
| E. Pereira et al. (2015) [37] | 22 HGSOC | Serum (ctDNA) | ddPCR, NGS, WES | TP53, PTEN, PIK3CA, MET, KRAS, FBXW7, BRAF | 93.8 | NR | 81-91 | 60-99 |
| A. Piskorz et al. (2016) [37] | 18 OC | Plasma (ctDNA) | Targeted NGS | TP53 | 100 | NR | NR | NR |
| R.C. Arend et al. (2018) [38] | 14 OC | Plasma (cfDNA) | Targeted NGS | 50 gene | 100 | NR | NR | NR |
| J.D. Cohen et al. (2016) [39] | 32 HGSOC | Plasma cfDNA (instability) |
WEG (WISECONDOR) | CNV | 38 | 40.6 | NR | 93.8 |
| A. Vanderst-ichele et al. [40] | 57 OC and bordline tumors | Plasma cfDNA | WGS | CNV | 67 | NR | NR | 99.6 AUC = 0.89 |
| Y. Wang et al. (2018) [34] | 245 OC | Cervix Pap brush samples (DNA) | Pap SEEK-PCR-based error-reduction technology Safe-SeqS, | 18 genes + assay for aneuploidy | NR | 33 | 34 | 99 |
| Tao Brush (DNA) | Pap SEEK-PCR-based error-reduction technology Safe-SeqS | 18 genes + assay for aneuploidy | NR | 45 | 47 | 100 | ||
| Salk et al. (2019) [41] | 10 OC | Uterine lavage (DNA) | Duplex Sequencing | TP53 | 80 | NR | 70 | 100 |
| E.Maritschnegg (2018) [42] | 33 OC | Uterine lavage (DNA) | Deep-sequencing | AKT1, APC, BRAF, CDKN2A, CTNNB1, EGFR, FBXW7, FGFR2, KRAS, NRAS, PIK3CA, PIK3R1, POLE, PPP2R1A, PTEN, TP53 | 80 for TP53 | NR | NR | NR |
| E.Maritschnegg (2015) [43] | 30 OC | Uterine lavage (DNA) | Massively parallel sequencing | AKT1, APC, BRAF, CDKN2A, CTNNB1, EGFR, FBXW7, FGFR2, | 60 for TP53 | 100 for TP53 | NR | NR |
| With ddPCR and SafeSeqS | KRAS, NRAS, PIK3CA, PIK3R1, POLE, PPP2R1A, PTEN, TP53 | 80 for TP53 | ||||||
| B.K Erickson et al. (2014) [44] | 5 OC | Vaginal tampon (DNA) | Massively parallel sequencing | NR | 60 | NR | 60 | NR |
| Kinde et al. (2013) [45] | 22 OC | Liquid Pap smear tests (DNA) | Massively parallel sequencing | NR | 41 | NR | NR | NR |
| N. Li et al (2019) [46] | 30 EOC | Plasma (CTC) | Magnetic nanospheres (MNs) + IHC | EpCAM, FRα | 92 | NR | 75 | 90 AUC = 0.8 |
| Zhang et al. (2018) [47] | 109 EOC | Plasma (CTC) | Imunomagnetic beads (EpCAM, HER2 and MUC1) + multiplex RT-PCR | EpCAM, HER2, MUC1, WT1, P16, PAX8 | 90 | 93 | NR | NR |
| Q Rao et al. (2017) [48] | 23 EOC | Plasma (CTC) | Microfluidic system with immunomagnetic beads (EpCAM) + IHC | EpCAM, CK3-6H5, panCK | 87 | NR | NR | NR |
| M. Lee et al. (2017) [49] | 54 EOC | Plasma (CTC) | Incorporating a nanoroughened microfluidic platform + IHC | EpCAM, TROP-2, EGFR, Vimentin, N-cadherin | 98.1 | NR | NR | NR |
| Dong Hoon Suh et al. (2017) [50] | 87 EOC, bordline, benigh | Plasma (CTC) | Tapered-slit membrane filters + IHC | EpCAM, CK9 | 56.3 | NR | 77.4 | 55.8 AUC = 0.61–0.75 |
| I. Chebouti et al. (2017) [51] | 95 EOC | Plasma (CTC) | Adna Test Ovarian Cancer and EMT-1 Select/Detect + Multiplex RT-PCR | EpCAM, ERCC1, MUC1, MUC16, PI3Ka, Akt-2, Twist | 82 | NR | >90 | >90 |
| K. Kolostova et al. (2016) [52] | 40 OC | Plasma (CTC) | MetaCell + IHC/qPCR | ICC: NucBlueTM, CelltrackerTM. EpCAM, MUC1, MUC16, KRT18, KRT19, ERCC1, WT1 |
58 | NR | NR | NR |
| K. Kolostova et al (2015) [53] | 118 OC | Plasma (CTC) | MetaCell + IHC/qPCR | ICC: NucBlueTM, CelltrackerTM. EpCAM, MUC1, MUC16, KRT18, KRT19, |
65.2 | NR | NR | NR |
| M. Pearl et al. (2015) [54] | 31 EOC | Plasma (CTC) | CAM uptake-cell enrichment + IHC/RT-qPCR | EpCAM, Ca 125, CD44, seprase EpCAM, CD44, MUC16, FAP |
100 | NR | 83 | 97 |
| Pearl et al. (2014) [55] | 129 EOC | Plasma (CTCs) | CAM uptake – cell enrichment + IHC | EpCAM, Ca 125, CD44, seprase | 88. 6 | 41.2 | 83 | 95.1 |
| Gao et al. (2015) [56] | 143 all 74 EOC | Serum microRNA | qRT-PCR | miR-200c | NR | NR | 72 | 70, AUC = 0.79 |
| miR-141 | 69 | 72, AUC = 0.75 | ||||||
| Meng et al. (2016) [57] | 163 EOC | Serum microRNA | TaqMan microRNA assays and ELISA | miR-200a | NR | NR | 83 | 90, AUC = 0.91 |
| miR-200b | 52 | 100, AUC = 0.81 | ||||||
| miR-200C | 31 | 100, AUC = 0.65 | ||||||
| 3miRNAs set | 88 | 90, AUC = 0.92 | ||||||
| Yokoi et al. in (2017) [58] | 269 all 155EOC | Serum microRNA | qRT-PCR + statistical cross-validation methods | 8 miRNA combination | NR | 86 | 92 | 91, AUC = 0.96 |
| Yokoi et al. in (2018) et al. [59] | EOC 333 | Serum microRNA | Microarrays | 10 miRNAs set miRNA-320a, -665, -1275, -3184-5p, -3185, -3195, -4459, 4640-5p, -6076, and -6717-5p. EOS vs. non cancer |
NR | NR | 99 | 100, AUC = 0.72–1.0 |
| Kim S. (2019) [60] | 68 all 39HGOC | Serum microRNA | qRT-PCR | miRNA-145 | NR | NR | 91.7 | 86.8, AUC = 86.8 |
| miRNA-200C | 72.9 | 90.0, AUC = 77.9 |
NR: not reported; OC- ovarian cancer; EOC: epithelial ovarian cancer; ddPCR: Droplet digital PCR; RT-PCR: real time PCR technology; qRT-PCR: quantitative real time PCR; NGS: next generation sequencing; CAM: cell adhesion matrix; WES: whole exome sequencing; TGS: targeted gene sequences; HGSOC: high grade serous ovarian cancer; ddPCR: droplet digital PCR; AUC- areas under the ROC curves; IHC: immunocytochemistry staging; CNV: Copy number variation; WES: Whole exome sequencing; Safe-SeqS: Safe-sequencing system; WGS: Whole genome sequencing.