Hypermethylated CDO1 and ZNF454 in Cytological Specimens as Screening Biomarkers for Endometrial Cancer

Wang, Lei; Dong, Lanlan; Xu, Jun; Guo, Lin; Wan, Kangkang; Wei, Jing; Zhao, Lanbo; Xue, Feng; Zhang, Kailu; Guo, Miao; Zou, Yuliang; Zhang, Lianglu; Li, Qiling

doi:10.3389/fonc.2022.714663

Cited by 5 publications

(6 citation statements)

References 40 publications

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“…of 0.83 and 0.90, respectively. In line with previous studies,17,24,32 CDO1 allowed endometrial cancer detection with excellent performance in all sample types tested (AUC 0.90-0.96). HAND2 performed moderately in all sample types (AUC 0.62-0.71), as opposed to previously described performances of 0.91 and 0.96 in vaginal swabs of stage IA and stage IB/II/III patients, respectively.…”

supporting

confidence: 90%

“…Finally, this comparative study had no access to paired samples from controls and did not include controls with postmenopausal bleeding symptoms or benign endometrial conditions. Even though others have shown that most of the markers tested in our study enable discrimination between benign endometrial pathology and cancer 17,18,20,21,23,24,32 , this was not validated in the current study.…”

Section: Discussionmentioning

confidence: 64%

“…Several discovery screens identified valuable hypermethylated genes as biomarker candidates for endometrial cancer detection in minimally invasive specimens 17‐19,21,23 . The markers ADCYAP1 , 18 BHLHE22 , 17 CDH13 , 18 CDO1 , 17,24,32 GALR1 21 and HAND2 23,24 tested in our study originate from such discovery screens carried out by different research groups. Except for CDO1 and HAND2 , none of these markers have been independently validated before for endometrial cancer detection in minimally‐ or noninvasive samples.…”

Section: Discussionmentioning

confidence: 97%

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DNA methylation testing for endometrial cancer detection in urine, cervicovaginal self‐samples and cervical scrapes

Wever

Helder

Splunter

et al. 2023

Intl Journal of Cancer

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Endometrial cancer incidence is rising and current diagnostics often require invasive biopsy procedures. DNA methylation marker analysis of minimally-and non-invasive sample types could provide an easy-to-apply and patient-friendly alternative to determine cancer risk. Here, we compared the performance of DNA methylation markers to detect endometrial cancer in urine, cervicovaginal self-samples and clinician-taken cervical scrapes. Paired samples were collected from 103 patients diagnosed with stage I to IV endometrial cancer. Urine and self-samples were collected at home. All samples were tested for nine DNA methylation markers using quantitative methylation-specific PCR. Methylation levels measured in endometrial cancer patients were compared to unpaired samples of 317 healthy controls. Diagnostic performances were evaluated by univariable and multivariable logistic regression analysis, followed by leave-one-out cross-validation. Each methylation marker showed significantly higher methylation levels in all sample types of endometrial cancer patients compared to healthy controls (P < .01). Optimal three-marker combinations demonstrated excellent diagnostic performances with area under the receiver operating curve values of 0.95 (95% CI: 0.92-0.98), 0.94 (0.90-0.97) and 0.97 (0.96-0.99), for endometrial cancer detection in urine, self-samples and scrapes, respectively. Sensitivities ranged from 89% to 93% at specificities of 90% to 92%.Virtually equal performances were obtained after cross-validation and excellent diagnostic performances were maintained for stage I endometrial cancer detection.Our study shows the value of methylation analysis in patient-friendly sample types

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supporting

confidence: 90%

Section: Discussionmentioning

confidence: 64%

Section: Discussionmentioning

confidence: 97%

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DNA methylation testing for endometrial cancer detection in urine, cervicovaginal self‐samples and cervical scrapes

Wever

Helder

Splunter

et al. 2023

Intl Journal of Cancer

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“…Similarly, previous reports documented 3-gene panel (BHLHE22-CDO1-CELF4/BHLHE22-CDO1-TBX5) or single gene-based (PCDHGB7) DNA methylation for EC detection using cervical scrapings, the ROC for these markers ranged from 0.80 to 0.94, or 0.86, respectively. 11 – 13 Also, Wang et al 26 reported a relevant study on methylation marker-based EC screening in endometrial cytological samples using Li Brush. Compared with endometrial sampling, cervical Pap brush sampling is a more acceptable screening tool for the general population.…”

Section: Discussionmentioning

confidence: 99%

Endometrial Cancer Detection by DNA Methylation Analysis in Cervical Papanicolaou Brush Samples

Wang,

Du,

et al. 2024

Technol Cancer Res Treat

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Background: Endometrial cancer (EC) is the leading gynecological cancer worldwide, yet current EC screening approaches are not satisfying. The purpose of this retrospective study was to evaluate the feasibility and capability of DNA methylation analysis in cervical Papanicolaou (Pap) brush samples for EC detection. Methods: We used quantitative methylation-sensitive PCR (qMS-PCR) to determine the methylation status of candidate genes in EC tissue samples, as well as cervical Pap brushes. The ability of RASSF1A and HIST1H4F to serve as diagnostic markers for EC was then examined in cervical Pap brush samples from women with endometrial lesions of varying degrees of severity. Results: Methylated RASSF1A and HIST1H4F were found in EC tissues. Further, methylation of the two genes was also observed in cervical Pap smear samples from EC patients. Methylation levels of RASSF1A and HIST1H4F increased as endometrial lesions progressed, and cervical Pap brush samples from women affected by EC exhibited significantly higher levels of methylated RASSF1A and HIST1H4F compared to noncancerous controls ( P < .001). Receiver operating characteristic (ROC) curves and area under the curve (AUC) analyses revealed RASSF1A and HIST1H4F methylation with a combined AUC of 0.938 and 0.951 for EC/pre-EC detection in cervical Pap brush samples, respectively. Conclusion: These findings demonstrate that DNA methylation analysis in cervical Pap brush samples may be helpful for EC detection, broadening the scope of the commonly used cytological screening. Our proof-of-concept study provides new insights into the field of clinical EC diagnosis.

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“…In summary, the use of DNA methylation testing in cervical cytology samples shows promise for the diagnosis of EC and AH. Two hypermethylated candidate genes, namely, cysteine dioxygenase type 1 (CDO1) and CUGBP Elav-like family member 4 (CELF4), have been identified as potential biomarkers for endometrial cancer (33,(37)(38)(39). As a key enzyme in cysteine catabolism, CDO1 belongs to the non-heme Fe(II) dioxygenase family.…”

Section: Introductionmentioning

confidence: 99%

Hypermethylated CDO1 and CELF4 in cytological specimens as triage strategy biomarkers in endometrial malignant lesions

Qi,

Sun,

et al. 2023

Front. Oncol.

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ObjectiveDeveloping a non-invasive and reliable triage test for endometrial malignant lesions is an important goal, as it could help to reduce the number of invasive diagnostic procedures required and improve patient survival. We aimed to estimate the diagnostic value of DNA methylation levels in cervical cytological samples of endometrial cancer (EC) and endometrial atypical hyperplasia (AH).MethodsA total of 607 women who had indications for endometrial biopsy in the Department of Obstetrics and Gynecology of Cangzhou Central Hospital from October 2022 to April 2023 were enrolled in this study. The cervical exfoliated cells were collected for gene methylation before endometrial biopsy. Clinical information, tumor biomarkers, and endometrial thickness (ET) of transvaginal ultrasonography (TVS) were also collected. With endometrial histopathology as the gold standard, multivariate unconditional logistic regression was applied to analyze the risk factors of endometrial malignant lesions. The role of cysteine dioxygenase type 1 (CDO1) and CUGBP Elav-like family member 4 (CELF4) gene methylation as a triage strategy biomarker in endometrial malignant lesions was specifically explored.ResultsMultivariate logistic regression analysis showed that premenopausal ET ≥ 11 mm or postmenopausal ET ≥ 5 mm, CDO1 ΔCt ≤ 8.4, or CELF4 ΔCt ≤ 8.8 were the risk factors for AH and EC, with odds ratios (ORs) (95%CI) of 5.03 (1.83–13.82) and 6.92 (1.10–43.44), respectively (p-values < 0.05). The sensitivity and specificity of CDO1/CELF4 dual-gene methylation assay for AH and EC reached 84.9% (95%CI: 75.3%–94.5%) and 86.6% (95%CI: 83.8%–89.5%), respectively. ET combined with DNA methylation detection further improved the specificity to (94.9%, 95%CI: 93.1%–96.8%).ConclusionThe accuracy of cervical cytology DNA methylation is superior to that of other clinical indicators in the non-invasive examination of endometrial malignant lesions. DNA methylation combined with TVS can further improve the specificity and is a promising biomarker triage strategy in women with suspected endometrial lesions.

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Hypermethylated CDO1 and ZNF454 in Cytological Specimens as Screening Biomarkers for Endometrial Cancer

Cited by 5 publications

References 40 publications

DNA methylation testing for endometrial cancer detection in urine, cervicovaginal self‐samples and cervical scrapes

DNA methylation testing for endometrial cancer detection in urine, cervicovaginal self‐samples and cervical scrapes

Endometrial Cancer Detection by DNA Methylation Analysis in Cervical Papanicolaou Brush Samples

Hypermethylated CDO1 and CELF4 in cytological specimens as triage strategy biomarkers in endometrial malignant lesions

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