Table 1.
The role of circulating cell-free tumor DNA (ctDNA) methylation in the detection of some common cancers.
| Cancer | Biomarker | Findings | Refs. |
|---|---|---|---|
| Colorectal cancer (CRC) | SEPT9 | The blood SEPT9 gene methylation assay exhibited better performance in a symptomatic population than in an asymptomatic population when compared with other colorectal cancer screening tests. | [119] |
| SEPT9-reinforced promoter DNA methylation in ctDNA was a significant discriminator between premalignant and malignant alterations in colorectal carcinogenesis. | [120] | ||
|
WIF1, NYP |
DNA methylation of WIF1 and NPY genes showed that hypermethylation of their gene promoters was detectable in both CRC tissue and corresponding ctDNA. | [121] | |
|
BCAT1, IKZF1 |
Post-surgery detection of methylated BCAT1 and IKZF1 in ctDNA in CRC patients was related to increased risk of residual disease and subsequently recurrence. | [122] | |
| Ovarian cancer |
RASSF1, BRCA1 |
Tumor cell-specific hypermethylation of BRCA1 and RASSF1A promoter regions were found in serum and peritoneal fluid from ovarian cancer patients. | [123] |
| Breast cancer |
WNT5A, KLK10, MSH2, SOX17, |
WNT5A, KLK10, MSH2, and SOX17 genes were found more frequently methylated in ctDNA in all the patient groups than in healthy individuals. More intense methylation of WNT5A gene correlated with greater tumor size, advanced disease, and poor outcome; SOX17 methylation was significantly correlated with the incidence of death, shorter progression-free survival, and overall survival, while KLK10 methylation was significantly correlated with unfavorable clinicopathological characteristics and relapse. | [124] |
|
APC, CCND2, FOXA1, PSAT1, RASSF1A, SCGB3A1 |
Methylated APC, CCND2, FOXA1, PSAT1, RASSF1A, and SCGB3A1 in ctDNA in breast cancer patients were confirmed as cancer-specific, although with variable performance. A panel combining four of them (APC, FOXA1, RASSF1A, and SCGB3A1) revealed the highest accuracy for disease detection (94%). | [125] | |
| Lung cancer |
CDO1, HOXA9, AJAP1, PTGDR, UNCX, MARCH11 |
Promoter methylation of a panel of six genes (CDO1, HOXA9, AJAP1, PTGDR, UNCX, and MARCH11) in ctDNA was found to have potential as a diagnostic and prognostic biomarker in non-small-cell lung cancer (NSCLC) patients. | [126] |
|
CALCA, HOXA9, RASSF1A, CDKN2A, DLEC1, CDH13, PITX2, WT1 |
Methylation levels of CALCA, HOXA9, RASSF1A, CDKN2A, DLEC1, CDH13, PITX2, and WT1 in ctDNA in patients with lung cancer were significantly higher than in the non-lung cancer group. Three of them (RASSF1A, CDKN2A, and DLEC1) were found only in lung cancer patients. | [127] | |
|
B3GAT2, BCAR1, HLF, HOPX, HOXD11, MIR1203, MYL9, SLC9A3R2, SYT5, VTRNA1-3 |
Using genome-wide plasma cfDNA methylation profiling, ten genes (B3GAT2, BCAR1, HLF, HOPX, HOXD11, MIR1203, MYL9, SLC9A3R2, SYT5, and VTRNA1-3) were identified as potential biomarkers for lung cancer. | [128] | |
| Prostate cancer |
GSTP1, APC |
Epigenetic markers GSTP1 and APC in circulating cell-free DNA have the potential to serve as prognostic markers for survival of castration-resistant prostate cancer patients. | [129] |
| Cholangiocarcinoma |
OPCML, HOXD9 |
cfDNA methylation of OPCML and HOXD9 may serve as a differential biomarker of cholangiocarcinoma and other biliary diseases. | [130] |
SEPT9, septin-9; WIF1, Wnt inhibitory factor 1; NYP, neuropeptide Y; BCAT1, branched-chain amino acid transaminase 1; IKZF1, IKAROS family zinc finger 1; RASSF1, Ras association (RaIGDS7AF-6) domain family number 1; BRCA1, breast cancer 1; WNT5A, Wnt family member 5A; KLK10, kallikrein-10; MSH2, mutS protein homolog 2; SOX17, SRY-box 17; APC, adenomatous polyposis coli; CCND2, cyclin-D2; FOXA1, forkhead box A1; PSAT1, phosphoserine aminotransferase 1; SCGB3A1, secretoglobin family 3A member 1; CDO1, cysteine dioxygenase type 1; HOXA9, homeobox A9; AJAP1, adherens junction-associated protein 1; PTGDR, prostaglandin D2 receptor; UNCX, UNC homeobox; MARCH11, membrane-associated ring-CH-type finger 11; CALCA, calcitonin-related polypeptide alpha; CDKN2A, cyclin-dependent kinase inhibitor 2A; DLEC1, DLEC1 cilia and flagella associated protein; CDH13, cadherin-13; PITX2, paired-like homeodomain 2; WT1, Wilms’ tumor suppressor gene; B3GAT2, beta-1,3-glucuronyltransferase 2; BCAR1, BCAR1 scaffold protein, Cas family member; HLF, hepatic leukemia factor; HOPX, HOP homeobox; HOXD11, homeobox D10; MIR1203, miR-1203; MYL9, myosin light chain 9; SLC9A3R2, SLC9A3 regulator 2; SYT5, synaptotagmin-5; VTRNA1-3, vault RNA 1-3; GSTP1, glutathione S-transferase pi 1; OPCML, opioid-binding protein/cell adhesion molecule-like; HOXD9, homeobox D9.