Table 2.
Summary of recent liquid biopsy-based DNA methylation studies in breast cancer
| Study (authors) | Cancer types | Markers | Sample | Detection method (s) | No. of cases | No. of controls | AUC | Sens (%) | Stage I/II Sens (%) | Spec (%) |
|---|---|---|---|---|---|---|---|---|---|---|
| For detection | ||||||||||
| Mijnes et al. [31] | Breast | SPAG6, NKX2-6, ITIH5, PER1 | Plasma | 450 K array, pyrosequencing | 111 | 14 | 0.729 | 63 | – | 80 |
| Moss et al. [72] | Breast | KRT19, LMX1B, ZNF296 | Plasma | TBS | 30 | 64 | 0.913 | 80 | – | 97 |
| Liu et al. [64] | Breast |
10 cfDNA markers (RYR2, RYR3, GABRB3, DCDC2 C, AC096570.1, LINC00923) |
Plasma | WGBS | 101 | 102 | 0.81 | – | – | – |
| Wang et al. [28] | Breast | CCDC181, GCM2, ITPRIPL1 | Plasma | EPIC (850 K) array, qMSP | 199 | 247 | 0.961 | 92.9 | – | 87.5 |
| Zhang et al. [43] | Breast | 26 cfDNA markers | Plasma | TBS | 204 | 129 | 0.945 | 87.76 | 87.5 | 92.73 |
| Gao et al. [13] | Breast | 15 ctDNA DMRs | Plasma | WGBS, ddPCR | 123 | 40 | 0.967 | 87 | – | 100 |
| Kresovich et al. [35] | Breast | 19 CpGs & 5 DNA methylation estimators | Blood | 450 K array | 1728 | 1375 | 0.69 | – | – | – |
| Chung et al. [122] | Breast | 49 genomic regions | Buffy coat | RRBS | 340 | 340 | 0.86 | – | – | – |
| Wang et al. [32] | Breast |
4 CpG markers (cg16652347, cg13828440, cg11754974 & cg18637238) |
PBMC | 850 K (EPIC) array, pyrosequencing, TBS | 491 | 290 | 0.918 | 80.3 | 85.7 | 89.1 |
| Lee et al. [34] | Breast | 51 CpG sites | Blood | EPIC array | 256 | 268 | 0.827 | 75 | – | 78 |
| Liu et al. [71] | Multiple (> 50 cancer types, including BC) | A classifier developed based on targeted methylation panel of > 100,000 methylation regions (refer to reference [71]) | Plasma | TBS | 2482 | 4207 | – | 54.9 | 18 (for all cancer types); < 5 (for BC) | 99.3 |
| Klein et al. [40] | Multiple (> 50 cancer types, including BC) | A refined assay and classifiers based on Liu et al. (refer to reference [40]) | Plasma | TBS | 2823 | 1254 | – | 51.5 | 16.8 (for all cancer types); 2.6 (for BC) | 99.5 |
| Jamshidi et al. [82] | Multiple (> 20 cancer types, including BC) | Whole-genome methylation classifier (refer to reference [82]) | Plasma | WGBS | 1628 | 1172 | 0.63 | 34 | – | 98 |
| Gao et al. [13] | Breast | 12 ctDNA DMRs | Plasma | WGBS | 78 (ER +) | 43 (ER−) | 0.780 | 73 | – | 87 |
| Manoochehri et al. [30] | Breast | 3 DMRs overlapping with SPAG6, LINC10606, TBCD/ZNF750 | Plasma | 450 K & EPIC arrays, ddPCR | 262 (TNBC) | 84 | 0.74 | – | – | – |
AUC area under the curve, BC breast cancer, ddPCR droplet digital PCR, DMRs differentially methylated regions, ER estrogen receptor, qMSP quantitative methylation-specific PCR, RRBS reduced representation bisulfite sequencing, Sens sensitivity, Spec specificity, TBS targeted bisulfite sequencing, TNBC triple-negative breast cancer, WGBS whole-genome bisulfite sequencing