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New Publication | CDO1/CELF4 Methylation Genes in Cervical Cytology Overcome the 'Inaccurate, Painful Examination' Dilemma of Endometrial Cancer

The incidence of endometrial cancer has been rising year by year, yet clinical diagnosis often faces the dilemma of "inaccurate imaging and painful biopsy." Recently, a team from Peking Union Medical College Hospital published an original study in the international authoritative journal Frontiers in Oncology, titled "Development and validation of hypermethylated gene markers in cervical cytological samples for detecting endometrial cancer (EndoMethy-I trial)."

This study successfully identified endometrial cancer-specific genes and validated CDO1/CELF4 gene methylation detection based on cervical cell sampling. This technology requires only a Pap smear-like sampling method to precisely capture carcinogenic signals, pushing endometrial cancer screening from "invasive surgery" to "molecular-level diagnosis."

I. Impressive Data: Sensitivity Exceeds 90%

The study showed that CDO1 and CELF4 were the most outstanding hypermethylated biomarkers. In the training set, the AUC (area under the curve) for endometrial cancer detection reached 0.93 and 0.91, respectively, demonstrating extremely strong discriminatory ability. In the validation set, the combined CDO1/CELF4 dual-gene detection achieved a sensitivity of 92.34% and specificity of 89.2%. In contrast, relying solely on endometrial thickness or CA125 often carries risks of excessive false positives or missed diagnoses.

The EndoMethy-I study not only confirmed the safety and effectiveness of cervical cell methylation detection but also, through the complementary strategy of "ultrasound for morphology, methylation for molecules," provided a novel non-invasive precision tool for early detection of endometrial cancer. With broader clinical adoption in the future, this will become an indispensable component of the women's health protection network.

Figure 1. Gene discovery workflow for endometrial cancer detection using CDO1/CELF4 methylation in cervical exfoliated cells

II. Clinical Implications

Based on the EndoMethy-I study findings, "ultrasound for morphology, methylation for molecules, complementary without missing diagnoses" has become the latest feasible clinical application. This "dual-track" workflow can optimize existing diagnostic procedures:

  1. Outpatient initial screening (morphology + molecular):

When patients present with abnormal bleeding, simultaneous performance of "transvaginal ultrasound (morphology)" and "methylation testing (molecular)" is recommended.

  • Both positive (ultrasound abnormal + methylation positive): Malignancy is highly suspected; immediate invasive examination should be arranged.

  • Normal morphology but positive molecular: Beware of "occult" lesions—do not let a normal ultrasound lower vigilance. Active follow-up or further examination is recommended.

  • Both negative: Safe return to routine follow-up can be recommended, significantly reducing endometrial cancer anxiety in symptomatic populations.

  1. Decision support for gray zones:

For postmenopausal women with endometrial thickness at the surgical threshold (e.g., 4–8 mm), or symptomatic women with atypical ultrasound results, methylation testing can provide critical "molecular evidence." Positive results warrant referral for specialist further examination; negative results can reduce the frequency of unnecessary invasive procedures.

III. Summary

The EndoMethy-I study not only confirmed the safety and effectiveness of cervical cell methylation detection but also, through the complementary strategy of "ultrasound for morphology, methylation for molecules," provided a novel non-invasive precision tool for early detection of endometrial cancer. With further validation through larger-scale clinical research data and broader adoption, this will become an indispensable component of the women's health protection network.

Reference

Chen X, Liu L, Jin X, Cheng Y, Wu H, You Y, Liou Y, Liu P, Lang J and Li (2026) Development and validation of hypermethylated gene markers in cervical cytological samples for detecting endometrial cancer (EndoMethy-I trial). Front Oncol. 16:1849730. doi: 10.3389/fonc.2026.1849730

About CISPOLY
CISPOLY · Beijing Origin-Poly
CISPOLY

Beijing Origin-Poly Co., Ltd. is a technology enterprise driven by innovation and committed to health. As a pioneer in the field of early diagnosis of gynecologic tumors, CISPOLY has developed early detection products for cervical cancer, endometrial cancer, ovarian cancer and other gynecologic malignancies based on proprietary technologies and patent-protected biomarkers, filling gaps in this field.

As women's awareness of their own health continues to grow, the women's health market holds tremendous potential. Beyond the gynecologic tumor early screening and diagnosis product line, CISPOLY will continue to establish additional women's health-related product pipelines, striving to become a technology innovation leader in the women's health market.