Diagnostic performance of CDO1 and ZSCAN12 methylation in endometrial versus cervical samples for endometrial cancer and atypical hyperplasia: a comparative study.
CDO1 and ZSCAN12 methylation markers showed strong diagnostic performance for endometrial cancer, with a sensitivity of 97.5% in the evaluated cases.
Where it sits
this study against the rest of the mgf (mechano growth factor) corpusSummary and findings
This study evaluated the diagnostic performance of CDO1 and ZSCAN12 methylation in paired endometrial and cervical samples for detecting endometrial cancer and atypical hyperplasia. A total of 127 women were analyzed, with 43 diagnosed with endometrial cancer, 13 with atypical hyperplasia, and 71 with benign conditions. The Em-based two-gene combination showed 97.5% sensitivity for endometrial cancer detection.
Abstract
<h4>Background</h4>This study evaluated the diagnostic performance of <i>CDO1</i> and <i>ZSCAN12</i> methylation in paired endometrial (Em) and exfoliated cervical (Cx) samples for detecting endometrial cancer (EC) and endometrial atypical hyperplasia (EAH).<h4>Methods</h4>We analysed 127 histologically confirmed women (43 EC, 13 EAH, 71 benign). Methylation levels were measured using bisulfite-conversion real-time PCR. Agreement, robustness, and diagnostic accuracy were assessed.<h4>Results</h4>Methylation levels increased stepwise from benign to EC across all sample types (all <i>p</i> < 0.001). For EC detection, <i>CDO1<sup>m</sup></i>_Em and <i>ZSCAN12<sup>m</sup></i>_Em achieved AUCs of 0.858 and 0.832, with ORs of 21.0 and 19.7, respectively. Bootstrap validation confirmed robustness. For the same sample source (Em or Cx), the clinical performance of <i>CDO1<sup>m</sup></i> and <i>ZSCAN12<sup>m</sup></i> was comparable (all <i>p</i> > 0.05). However, significant differences were noted between Em and Cx samples for <i>ZSCAN12<sup>m</sup></i>'s negative predictive value (NPV) in EC detection (<i>p</i> = 0.045), and for <i>CDO1<sup>m</sup></i>'s sensitivity, NPV, and negative likelihood ratio (nLR) in EAH/EC detection (<i>p</i> = 0.029, 0.026, and 0.031, respectively). The Em-based two-gene combination showed 97.5% sensitivity for EC (39 of 40 evaluable cases), failing to detect only 1 of 40 cases.<h4>Conclusions</h4><i>CDO1</i> and <i>ZSCAN12</i> methylation demonstrated robust diagnostic performance for EC and EAH. The Em-based two-gene combination showed excellent sensitivity. Most diagnostic metrics were comparable between sample sources, with Em showing advantages specifically in NPV-related measures. Given that these differences may be assay-dependent and that most performance metrics showed no significant differences, cervical sampling remains a promising less invasive option but warrants cautious interpretation and further validation.