CDO1/CELF4 Methylation for EC Screening in Premenopausal AUB

1Background & Objective

Problem: AUB is common but few have EC; TVS & CA125 limited; invasive hysteroscopy over-used.
Objective: validate CDO1m/CELF4m screening in premenopausal AUB, alone & combined with BMI/ET.

2Study Design & Cohort

296

premenopausal AUB

2021.11–22.10

enrollment

hysteroscopy

gold standard

Setting: Third Xiangya Hospital OB/GYN; consecutive premenopausal AUB.
Assays: ThinPrep cervical cells → CDO1m/CELF4m; TVS ET; serum CA125.
Readout: CDO1m ΔCt ≤8.4 · CELF4m ΔCt ≤8.8 · dual = either positive.
Analysis: univariate logistic (OR) · ROC/AUC · subgroup by BMI & ET.
Cut-offs: BMI ≥25 · ET ≥11 mm (premenopausal proliferative phase).

64.49

CDO1m OR (20.5–203.3)

42.53

dual OR (11.9–152.0)

12.79

CELF4m OR (4.9–33.3)

dual Se

85.7%

dual Sp

87.6%

Se 85.7%

dual · sensitivity

Sp 87.6%

dual · specificity

AUC 0.955

best combo

AUB spectrum: menorrhagia · cycle irregularity · intermenstrual spotting.
Outcome: EC confirmed by hysteroscopic histology in this cohort.
Why premenopausal AUB: younger EC is rising; TVS thresholds controversial in this group.
CA125: classic marker but low accuracy — included for comparison.
Reuse: ThinPrep sample also serves cytology — no extra collection.
Protection: fewer unnecessary hysteroscopies preserves fertility & reduces burden.

Best model: BMI <25 + ET + dual methylation AUC 0.955 — near-perfect screening.
Independent value: each methylation marker significant even after BMI/ET adjustment.

Methylation outperformed other non-invasive indicators in this premenopausal AUB cohort; combining with BMI or ET further improves screening.

3Risk Factors — OR Comparison

CDO1m

OR 64.49

Dual-gene

OR 42.53

CELF4m

OR 12.79

ET ≥11 mm

OR 8.41

BMI ≥25

OR 4.76

Methylation dominates: CDO1m OR 64.49 (20.46–203.33) — far above ET/BMI.

4ROC & Dual-Gene Performance

ROC curves of methylation, ET and combinations

Fig. ROC — ET, single/dual methylation & combined models for EC screening.

85.7%

Se · dual

87.6%

Sp · dual

Best balance: dual-gene methylation highest Se/Sp among single tests.
Combination: dual + BMI or ET lifts screening efficiency further.

5Subgroup Combined AUC

0.955

BMI <25 · ET+dual

0.898

BMI ≥25 · ET+dual

0.938

ET ≥11 · BMI+dual

0.906

ET <11 · BMI+dual

Consistently high: combined models reach AUC 0.90–0.96 in every subgroup.
Practical: methylation + TVS/BMI is a simple clinic-based screening step.