Table 1. Gene methylation in ctDNA of lung cancer patients.
| Purpose | Material | Analytical method | Gene promoter | Number of cases (stage) | Number of controls | Sensitivity/Specificity or main findings (%) | References |
|---|---|---|---|---|---|---|---|
| Diagnosis | Plasma | qMSP | SHOX2 | 222 (I–III) | 189 | 60/90 | (46) |
| Diagnosis | Plasma (from 7 mL blood) | qMSP | SHOX2 | 38 (I–IV) | 31 | 80.65/78.57 | (44) |
| Diagnosis | Plasma (1 mL) | qMSP | RASSF1A and RARB2 | 60 (I–III) | 32 | 87/75 | (49) |
| Diagnosis | Plasma (>3.5 mL) | qMSP | DCLK1 | 65 (II–IV) | 95 | 49.2/91.6 | (47) |
| Diagnosis | Plasma (4 mL) | qMSP | SEPT9 | 70 (II–IV) | 100 | 44.3/92.3 | (48) |
| Prognosis | Plasma (200 µL) | qMSP | BRMS1 | 48 (I–III) and validation with 74 (IV) | 24 | BMRS1 promoter methylation had a negative impact on survival | (50) |
| Prognosis | Plasma (200 µL) | qMSP | SOX17 | 48 (I–III) and validation with 74 (IV) | 24 | SOX17 promoter methylation had a negative impact on survival | (43) |
| Prognosis | Plasma (>3.5 mL) | qMSP | DCLK1 | 65 (II–IV) | 95 | DCLK1 promoter methylation had a negative impact on survival | (47) |
| Prognosis | Serum (800 µL) | qMSP | SFN | 115 (III–IV) | — | SFN promoter methylation had a positive impact on survival | (51) |
| Therapy monitoring | Plasma | qMSP | RASSF1A and APC | 316 (III–IV) | — | Elevated level of methylation 24 h after chemotherapy correlated with good response to cisplatin | (52) |
| Therapy monitoring | Plasma (3.5 mL) | qMSP | SHOX2 | 36 (III–IV) | — | Better survival in patients with low SHOX2 promoter methylation one week after the start of chemotherapy | (53) |
| Therapy monitoring and disease recurrence | Plasma | qMSP | RASSF1A and RARB2 | 43; 26 | — | - Reduced concentration of the methylated alleles after neoadjuvant chemotherapy and surgery; increased concentration of at least one methylated allele in patient with disease recurrence | (49) |
| Prediction of response to therapy | Serum (800 µL) | qMSP | CHFR | 366 (IV) | — | Patients with unmethylated CHFR had better survival with second-line EGFR TKIs, compared to chemotherapy | (54) |
SHOX2, short stature homebox 2; RASSF1A, ras association domain family 1 isoform A; RARB2, retinoic acid receptor B2; DCLK1, doublecortin like kinase 1; SEPT9, septin9; BRMS1, breast cancer metastasis suppressor-1; SOX17, (sex determining region Y)-box 17; APC, adenomatous polyposis coli; CHFR, checkpoint with forkhead and ring finger domains; qMSP, quantitative methylation-specific PCR.