Table 9.
Non-invasive epigenetic DNA methylation biomarkers for ovarian cancer.
| Epigenetic marker(s) | Source | Patient/sample | Clinical prediction | Technology | References |
|---|---|---|---|---|---|
| Methylation of ≥1 gene of BRCA1, RASSF1A, APC, p14ARF, p16INK4A, or DAPK | Serum and cytologically negative peritoneal fluid | 50 serum, 40 peritoneal fluid from EOC patients along with 40 control serum and peritoneal fluid samples | Presence of malignancy Sensitivity: 41/50 (82% for serum) 28/30 (93% for peritoneal fluid), Specificity: 100% (all tumor stages). |
Methylation-specific-PCR (MSP) | Ibanez de Caceres et al., 2004 |
| DAPK | Whole peripheral blood DNA | 26 peripheral blood samples | Sensitivity: 14/16 (54%) for DAPK-methylation-positive samples: Specificity: 10/10 (100%) for DAPK methylation negative |
Methylation-specific PCR (MSP) | Collins et al., 2006 |
| Methylation of ≥1 gene of SOX1, PAX1 or SFRP1 | Serum | 46 (26 ovarian cancer cases and 20 patients with a benign condition | Sensitivity: 73.08% Specificity: 75% | Methylation-specific PCR (MSP) | Su et al., 2009 |
| Methylation of 7-gene panel (APC, RASSF1A, CDH1, RUNX3, TFPI2, SFRP5, and OPCML | Serum | 202 patients (87 EOC cases, 53 benign cases and 62 controls) | Sensitivity of 7-gene panel: 85.3% Specificity of 7-gene panel: 90.5% in stage I EOC Sensitivity of CA125: 56.1% Specificity of CA125: 64.15% |
Multiplex methylation-specific PCR (MSP) | Zhang et al., 2013 |
| 10-gene panel (Combination of BRCA1, HIC1,PAX5,PGR, THBS1) | Plasma | 66 (33 cancer cases and 33 control) | Presence of malignancy Sensitivity: 61% Specificity: 85% |
Microarray based multiplex assay(MethDet56 technique) | Melnikov et al., 2009 |
| Several gene panel (RASSF1A and PGR-PROX) (RASSF1A, CALCA and EP300) |
Serum | 90 (30 EOC cases, 30 cases with Benign disease along with 30 controls non neoplastic samples) | Methylation of RASSF1A and PGR-PROX Sensitivity: 80.0% Specificity:73.3% Methylation of RASSF1A, CALCA and EP300 Sensitivity: 90.0% Specificity: 86.7%. |
Microarray based Assay(MethDet 56) | Liggett et al., 2011 |
| OPCML | Serum | 194 (71 EOC, 43 benign and 80 controls non neoplastic samples) | Sensitivity: 87.18% Specificity: 93.75% Accuracy: 90.14% |
Nested Methylation -specific PCR (MSP) | Wang et al., 2017 |
| RASSF1A | Plasma | 53 samples including OC tumors, adjacent tumor cell free tissues and paired plasma circulating tumor DNA | Sensitivity: 33/53 (62.3%), RASSF1A methylation of paired plasma CtDNA showed slight concordant with primary tumor samples (P = 0.227, 2-sided Pearson χ2 test, k = 0.156). Significantly correlates with overall survival |
Real-time methylation specific-PCR (real-time MSP) and methylation-sensitive high-resolution melting analysis (MS-HRMA) | Giannopoulou et al., 2017 |
| ESR1 | Plasma | Group A: 66 OC cases Group B: 53 OC case along with 50 paired plasma samples |
Sensitivity of detection: 38%. ESR1 methylation predicted better clinical outcomes: overall survival (P = 0.027), progression-free survival (P = 0.041) |
Real-time methylation-specific PCR (real-time MSP) assay | Giannopoulou et al., 2018 |
| 3-gene panel | Serum | For assay development: 151 cases and for validation study 250 cases with different conditions in 3 sets | Pre-chemotherapy Sensitivity: 41.4% Specificity: 90.7% Post chemotherapy Responders: 78% non-responders: 86% |
Targeted ultra-high coverage bisulfite sequencing | Widschwendter et al., 2017 |