Natl Med J China · 2023;103(12):907–912 · Cross-Sectional · China

DNA Methylation for Postmenopausal EC Screening

DNA 甲基化检测在绝经后女性子宫内膜癌筛查中的应用价值
143 postmenopausal women (56 EC + 87 controls) · dual-gene Se 87.5% / Sp 90.8% · TVS+DNA Se 100% · CELF4m OR 44.01
Kong L, Xiao X, Wan R, Chao X, Chen X, Wang J, Wu H, Li L
Peking Union Medical College Hospital · 中华医学杂志 2023;103(12):907–912 · doi:10.3760/cma.j.cn112137-20220929-02058
143
postmenopausal (56 EC)
87.5%
dual Se
90.8%
dual Sp
100%
TVS + DNA Se

1Background & Objective

  • Problem: no non-invasive EC screening recommended; invasive assessment has high miss rates.
  • Objective: value of cervical cell CDO1m/CELF4m ± TVS for postmenopausal EC screening.

2Study Design & Cohort

56
EC · 59.3y
87
control · 61.1y
2020.5–21.10
enrollment
  • Setting: PUMCH; postmenopausal women, suspected lesions, hysteroscopy-referred.
  • Assays: cervical cells → CDO1m/CELF4m (ΔCt ≤8.4 / ≤8.8) + TVS ET + CA125.
  • Reference: hysteroscopic histopathology = gold standard.
  • Inclusion: ≥40 y postmenopausal; suspected lesion per guideline; consent.
  • Cut-offs: TVS positive ET ≥5 mm · CA125 ≥35 U/ml.
87.5%
dual Se (75.9–94.8)
90.8%
dual Sp (82.7–95.9)
100%
TVS+DNA Se
100%
NPV · TVS+DNA
61.5%
PPV · TVS+DNA
86.0%
PPV · dual
TVS+DNA Se
100%
TVS+DNA Sp
59.8%
P=0.051
age EC vs control
≥40y
inclusion age
  • Design note: TVS + DNA maximal sensitivity; dual alone best specificity balance.
  • Practice fit: fits opportunistic screening for postmenopausal bleeding workup.
  • First exfoliated-cell epigenetics study for EC screening in China — novel approach.
  • Why not blood ctDNA: low tumor-cell abundance lacks sensitivity for early EC.
  • Cell advantages: fully non-invasive · easy collection · ample cells · histology-concordant.
  • Gene choice: CDO1/CELF4 distinguish EC from cervical lesions & subtypes.
Ethics ZS-2740 · cross-sectional design · multivariable logistic + ROC.

3Risk Factors — OR Comparison

CELF4m
OR 44.01
CA125 ≥35
OR 33.23
CDO1m
OR 17.34
ET ≥5 mm
OR 14.45
Postmeno bleeding
OR 8.41
  • Methylation leads: CELF4m OR 44.01 (6.79–285.25) & CDO1m 17.34 — above CA125/ET.

4Dual-Gene & TVS Combination

87.5%
Se · dual
90.8%
Sp · dual
86.0%
PPV
91.9%
NPV
100%
Se · TVS+DNA
59.8%
Sp · TVS+DNA
100%
NPV · TVS+DNA
  • TVS + DNA: sensitivity reaches 100% — no EC missed; specificity drops to 59.8%.

5ROC — Screening Accuracy

ROC curves for EC screening indicators
Fig. ROC — dual-gene methylation vs TVS & other indicators.
AUC↑
dual best single
100%
TVS+DNA Se
  • Accuracy: methylation outperforms other non-invasive indicators in postmenopausal women.
  • Balanced default: dual-gene alone (Se 87.5/Sp 90.8) — good specificity for triage.
Clinical Significance