Chin J Lab Med · 2023;46(4):367–374 · Prospective · China

CDO1/CELF4 Methylation for EC in Childbearing-Age AUB

DNA 甲基化检测在育龄期异常子宫出血女性子宫内膜癌诊断中的应用价值
517 childbearing-age AUB women · dual-gene OR 87.39 · Se 91.7% / Sp 88.8% · AUC 0.90 · TVS+DNA Se 95.8%
Zhao X, Xu D, Ma J, Fu Y, Li B, Jin X, Liu Y, Liu P
Third Xiangya Hospital, Central South University · 中华检验医学杂志 2023;46(4):367–374
517
childbearing AUB
OR 87.39
dual-gene
91.7%
Se · dual
0.90
AUC · dual

1Background & Objective

  • Problem: EC now #2 female genital malignancy in China; childbearing-age AUB needs non-invasive triage.
  • Objective: value of CDO1m/CELF4m on cervical cells for EC detection in childbearing-age AUB.

2Study Design & Cohort

517
AUB + hysteroscopy
2021.11–22.10
enrollment
hysteroscopy
gold standard
  • Setting: Third Xiangya Hospital gynecology; prospective childbearing-age AUB.
  • Assays: cervical cells → cytology · HPV · CDO1m/CELF4m (ΔCt ≤8.4/≤8.8) + TVS ET + CA125/CA199.
  • Reference: hysteroscopic histopathology = gold standard.
  • OR model: age 1.16 · BMI≥25 4.33 · ET≥11 9.49 · CDO1m 69.62 · CELF4m 23.64 · dual 87.39.
  • Comparison: CA125/CA199 · cytology · HPV — not significant between groups.
91.7%
Se · 95%CI 80.6–100
88.8%
Sp · 95%CI 86.0–91.6
0.90
AUC · 95%CI 0.83–0.97
dual Se
91.7%
dual Sp
88.8%
95.8%
TVS+DNA Se
68.0%
TVS+DNA Sp
99.7%
TVS+DNA NPV
  • Clinical picture: AUB / abnormal discharge — main symptoms prompting hysteroscopy.
  • Marker check: CA125/CA199 did not differ — methylation adds unique signal.
  • Inclusion: childbearing-age AUB with hysteroscopy indication; consent.
  • Exclusion: pregnancy/lactation · prior treatment · other malignancy.
  • Sample: ThinPrep cervical cells pre-op — cytology/HPV/methylation in one sample.
  • Limits: single-center; PPV moderate (28.9%) in low-prevalence cohort.
Dual-gene AUC 0.90 (0.83–0.97) — highest among all indicators tested; TVS+DNA Se 95.8%.

3Risk Factors — OR Comparison

Dual-gene
OR 87.39
CDO1m
OR 69.62
CELF4m
OR 23.64
ET ≥11 mm
OR 9.49
BMI ≥25
OR 4.33
  • Methylation dominates: dual-gene OR 87.39 (24.83–555.05) — far above ET/BMI.

4Performance Matrix & TVS

91.7%
Se · dual
88.8%
Sp · dual
28.9%
PPV
99.5%
NPV
95.8%
Se · TVS+DNA
68.0%
Sp · TVS+DNA
99.7%
NPV · TVS+DNA
  • NPV 99.5%+: negative methylation safely defers hysteroscopy in young women.
  • TVS+DNA: Se 95.8% — near-complete EC capture; specificity 68.0%.

5ROC — AUC Ladder

ROC curves for EC screening indicators
Fig. ROC — dual-gene methylation highest (AUC 0.90) vs single genes, ET & BMI.
Dual-gene
AUC 0.90
CDO1m
0.87
CELF4m
0.81
ET ≥11
0.75
BMI ≥25
0.67
  • Clear separation: methylation AUC ≫ ultrasound/BMI — best non-invasive discriminator.
Clinical Significance