Table 1.
Diagnostic and prognostic significance of the L1 methylation status in cancer.
| Cancer Type | Methods | Diagnostic Value (*) | Prognostic Value | Ref. |
|---|---|---|---|---|
| Breast cancer | Pyrosequencing | Normal tissues—92%, IBC tissues—86% |
L1 hypomethylation was significantly associated with decreased OS (HR 2.19, 95% CI 1.17–4.09), decreased DFS (HR 2.05, 95% CI 1.14–3.67), and increased DR (HR 2.83, 95 % CI 1.53–5.21) in younger (≤55 years) but not in older patients (>55 years) | [54] |
| Pyrosequencing | Normal tissues—64%, IBC tissues—61% |
- | [55] | |
| Hepatocellular carcinoma | Bisulfite-specific PCR and DNA sequencing analysis | Normal tissues—60%, tumor tissues—34% |
Patients with L1 hypomethylation had decreased median postresection TFS (22 months [95% CI: 13.3–30.7]) and OS (35 months [95% CI: 24.0–46.1]) compared to those with L1 hypermethylation (40 and 60 months, respectively) | [56] |
| Pyrosequencing | Normal tissues—68%, tumor tissues—48% |
- | [57] | |
| Normal tissues—57%, tumor tissues—46% |
- | [58] | ||
| Esophageal cell carcinoma | Pyrosequencing | Normal tissues—82%, tumor tissues—64% | - | [59] |
| Normal tissues—79%, tumor tissues—63% | L1 methylation was significantly associated with DFS (univariate HR 2.32, 95% CI 1.38–3.84, methylation level [quartile] < 56%; multivariate HR 1.81, 95% CI 1.06–3.05) and CSS (univariate HR 2.21, 95% CI 1.33–3.60; multivariate HR 1.87, 95% CI 1.12–3.08) | [60] | ||
| Quantitative real-time MSP | Normal tissues—90%, tumor tissues—78% | Cumulative survival was significantly shorter for ESCC patients with L1 methylation level ≤ 78% than for those with > 78% (34 vs. 43 months) | [61] | |
| Colorectal cancer | Pyrosequencing | Normal tissues—77%, tumor tissues—57% | OS was significantly longer in patients with L1 methylation level ≥ 65% | [62] |
| MSP-PCR, pyrosequencing after assay validation | - | L1 hypomethylation was significantly associated with higher CRC-specific mortality (for 10% decrease in L1 methylation: HR 2.45, 95% CI 1.64–3.66) | [63] | |
| MethyLight assay | - | PFS, OS, and 5-year OPS were significantly shorter in patients with low L1 methylation than in those with high L1 methylation (HR 1.00 vs. HR 2.74 [95% CI 1.19–6.29]) | [64] | |
| Quantitative PCR | - | L1 hypomethylation was significantly associated with lower OS (HR 1.68, 95% CI 1.03–2.75); the association was stronger in patients > 65 years (HR 2.00, 95% CI 1.13–3.52) | [65] | |
| Gastric and colon cancers | Pyrosequencing | Colon: normal tissues—67%, tumor tissues—61% Gastric: normal tissues—66%, tumor tissues—62% |
- | [66] |
| Gastric cancer | Pyrosequencing | Chronic gastritis—62%, cancer—52% | L1 hypomethylation level (<51%) was significantly associated with shorter DFS and OS | [67] |
| Lung cancer | Pyrosequencing | Normal tissues—74%, ADC tissues—67% | Patients with low L1 methylation levels (19–69%) had significantly higher recurrence rates and shorter DFS compared to those with high methylation levels (74–81%) | [68] |
| - | L1 hypomethylation (<52%) was significantly associated with lower survival rates in patients with ADC stage I | [69] | ||
| Bisulfite-PCR, pyrosequencing | Normal tissues—70%, ADC tissues—63%, SCC tissues—38% |
L1 hypomethylation (≤58%) was independently associated with poor prognosis (p = 0.025) | [70] | |
| Oropharyngeal squamous cell carcinoma | Quantitative MSP-PCR | - | L1 hypomethylation (<50% vs. ≥70%) was significantly associated with higher risk of early disease relapse (OR = 3.51; 95% CI 1.03–12.00) | [71] |
Abbreviations: IBC, invasive breast cancer; CRC, colorectal cancer; ESCC, esophageal squamous cell carcinoma; OS, overall survival; DFS, disease-free survival; DR, distant recurrence; TFS, tumor-free survival; OPS, overall probability of survival; CSS, cancer-specific survival; PFS, progression-free survival; SCC, squamous cell carcinoma; ADC, adenocarcinoma. *—Diagnostic value is considered according to L1 MI.