Chin J Lab Med · 2024;47(4):401–406 · Case-Control · China

Serum cfDNA CDO1/HOXA9 Methylation for Ovarian Cancer

血清中 CDO1 基因与 HOXA9 基因启动子甲基化高表达在卵巢癌诊断中的意义
151 women (29 OC + 122 benign) · dual AUC 0.936 · Se 89.7% / Sp 97.5% · early stage 12/14 · adjusted OR 31.75
Hou Q, Yuan Y, Li Y, Gong Z, Zhang Q, Feng D, Gong Y, Wang L, Liu P, Xie X, He L
Chengdu Women & Children Central Hospital · 中华检验医学杂志 2024;47(4):401–406
151
ovarian mass (29 OC)
0.936
AUC · dual
89.7%
Sensitivity
97.5%
Specificity

1Background & Objective

  • Problem: OC #3 incidence / #2 mortality among female genital cancers; stage I 5y-survival 90% vs IV 20%.
  • Objective: cfDNA CDO1/HOXA9 methylation for OC detection & stratified management.

2Study Design & Cohort

29
ovarian cancer
122
benign
2022.1–23.10
enrollment
  • Setting: Chengdu Women & Children Central Hospital; mass surgery indication.
  • Assays: serum CA125 · HE4 · ROMA · cfDNA CDO1/HOXA9 methylation.
  • Reference: laparoscopic ovarian histopathology = gold standard.
  • Profile: 98.4% benign premenopausal vs 75.9% OC postmenopausal.
31.75
adj. OR dual (1.84–1084.3)
343.78
unadj. OR dual
124.67
unadj. OR ROMA
0.936
AUC (0.878–0.994)
89.7%
Se (73.6–96.4)
97.5%
Sp (93.0–99.2)
  • cfDNA advantage: repeatable blood draw — dynamic monitoring possible.
  • Stratified care: methylation(+) → aggressive work-up; (−) → benign follow-up.
Dual methyl · unadj
OR 343.78
ROMA · unadj
OR 124.67
  • Inclusion: ovarian mass surgery indication; complete clinical data.
  • Exclusion: prior treatment · other malignancy · invalid samples.
  • Statistics: Mann-Whitney U · Fisher exact · logistic (OR) · ROC/AUC.
  • Blood vs tissue: cfDNA avoids invasive ovarian biopsy.
After adjusting age/menopause/ROMA, dual-methylation(+) carries 31.75× OC risk; ROC DeLong P for AUC comparisons.

3AUC Ladder — All Markers

Dual methyl
0.936
ROMA
0.867
CDO1m
0.819
HE4
0.776
HOXA9m
0.764
CA125
0.704
  • Methylation on top: dual AUC 0.936 ≫ ROMA & all serological markers.

4Dual-Gene Performance

0.936
AUC (0.878–0.994)
89.7%
Se (73.6–96.4)
97.5%
Sp (93.0–99.2)
31.75
adj. OR
  • Blood-based: cfDNA methylation — simple liquid biopsy, no tissue needed.
  • High specificity: 97.5% — few false positives among benign masses.

5Detection by FIGO Stage

Early I–II · dual
12/14
Early · CA125
10/14
Early · ROMA
9/14
Late III–IV · dual
9/10
12/14
early I–II · dual
10/14
early · CA125
9/14
early · ROMA
9/10
late III–IV · dual
  • Early detection: dual-methylation best at stage I–II (12/14) — key for survival.
  • Late stage: 9/10 positive — stays the best marker.
  • All scenarios: dual + ROMA + CDO1m + CA125 positive in metastatic/unstaged cases.
  • Why blood: cfDNA repeatable & patient-friendly — complements tissue diagnosis.
Clinical Significance