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

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

JOURNAL=Frontiers in Oncology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.714663

DOI=10.3389/fonc.2022.714663

ISSN=2234-943X

ABSTRACT=<p>We aimed to estimate the diagnostic value of DNA methylation levels in cytological samples of endometrial cancer (EC) and atypical hyperplasia (AH). Two hypermethylated genes, namely, cysteine dioxygenase type 1 (<italic>CDO1</italic>) and zinc finger protein 454 (<italic>ZNF454</italic>), in patients with EC were identified from The Cancer Genome Atlas database. In 103 endometrial histological specimens (the training set), the methylation levels of candidate genes were verified by quantitative methylation-specific polymerase chain reaction (qMSP). The methylation levels of another 120 cytological specimens (the testing set) were evaluated. Sensitivity (Se), specificity (Sp), accuracy, and area under the curve (AUC) were determined, with diagnosis verified by histopathological results. <italic>CDO1</italic> and <italic>ZNF454</italic> verified hypermethylation in histological specimens of patients with EC and AH compared with those with benign and normal endometrium (<italic>P</italic> &lt; 0.001). In cytological specimens, hypermethylated <italic>CDO1</italic> showed 86.36% Se and 90.79% Sp with the cutoff value of 6.0 to distinguish between malignant and benign groups; <italic>ZNF454</italic> showed 79.55% Se and 93.42% Sp with the cutoff value of 7.1. When the two genes were combined, Se increased to 90.91% and Sp was 86.84%. AUC reached 0.931 (95% CI: 0.885–0.976). The diagnostic accuracy with cytology had no significant difference with endometrial tissue (<italic>P</italic> = 0.847 for <italic>CDO1</italic>, <italic>P</italic> = 0.108 for <italic>ZNF454</italic>, and <italic>P</italic> = 0.665 for their combination). Hypermethylated <italic>CDO1</italic> and <italic>ZNF454</italic> in endometrial cytology showed high Se, Sp, and AUC to detect EC and AH. Methylation analysis of endometrial cytology is promising biomarker for the screening of EC and AH.</p>