What question did this study set out to answer?

This study aims to assess the effectiveness of DNA methylation biomarkers in detecting endometrial cancer through cervical exfoliated cells.

June 3, 2026Open Access

Non-invasive detection of endometrial cancer through exfoliated cervical cell gene methylation signatures: Evaluation of CELF4/GALR1/ZNF486 methylation biomarkers

Key Points

This study aims to assess the effectiveness of DNA methylation biomarkers in detecting endometrial cancer through cervical exfoliated cells.
Case-control design involving 104 women with different endometrial conditions from September 2024 to June 2025.
Quantitative methylation-specific polymerase chain reaction was used to measure biomarker performance against histopathological results.
Evaluation of CELF4, GALR1, and ZNF486 methylation levels in cervical samples for diagnostic accuracy.
All biomarkers showed significant ΔCp value differences between benign lesions and endometrial cancer (P < 0.01).
GALR1 methylation had better specificity (60.9%) compared to transvaginal ultrasound measurements (27.5%, P < 0.001).
Model 3 (three-gene panel) showed the highest overall diagnostic performance with AUC 0.733 and sensitivity 91.4%.

Abstract

Objective: The current non-invasive screening methods for endometrial cancer (EC), such as transvaginal ultrasound (TVUS), lack sufficient specificity, leading to unnecessary invasive diagnostic procedures. The detection of cancer-specific deoxyribonucleic acid (DNA) methylation alterations in cervical cytology samples presents a promising, minimally invasive alternative. This study aimed to evaluate the diagnostic potential of novel DNA methylation biomarkers (CUGBP Elav-like family member 4 methylation CELF4 m , Galanin receptor 1 methylation GALR1 m , Zinc finger protein 486 methylation ZNF486 m ) in cervical exfoliated cells for EC screening. Material and Methods: This case–control study enrolled patients scheduled for diagnostic or surgical curettage at the hospital from September 2024 to June 2025. A total of 104 women underwent endometrial evaluation (32 type I EC, 3 type II EC, 61 benign lesions BL, 8 atypical hyperplasia). Quantitative methylation-specific polymerase chain reaction assessed biomarker performance against histopathological diagnosis. Results: All three markers ( CELF4 m , GALR1 m , ZNF486 m ) showed significant differential ΔCp values between BL and EC groups (all P < 0.01), with moderate diagnostic accuracy (area under the ROC curve AUCs: 0.654-0.704). The single-marker GALR1 m outperformed endometrial thickness (ET) measured by TVUS in specificity (60.9% vs. 27.5%, P < 0.001) while maintaining comparable sensitivity (80.0% vs. 74.3%, P = 0.527). A two-marker panel ( GALR1 m / ZNF486 m , Model 1) achieved sensitivity (97.1% 95% confidence interval [CI: 91.6–100%]) with modest specificity (49.3% 95% CI: 37.5-61.1%). Among three-gene models, Model 3 demonstrated the highest overall performance (AUC: 0.733 95% CI: 0.657-0.808; sensitivity: 91.4% 95% CI: 82.1-100%), whereas Model 4 balanced sensitivity (80.0% 95% CI: 66.7-93.3%) and improved specificity (63.8% 95% CI: 52.4-75.1%). Conclusion: DNA methylation signatures in cervical cells show superior diagnostic accuracy to conventional ET measured by TVUS, particularly through multi-marker panels. This non-invasive approach represents a promising EC screening strategy.

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