Genome-wide methylation profiling identified methylated KCNA3 and OTOP2 as promising diagnostic markers for esophageal squamous cell carcinoma

作     者：Bian Yan Gao Ye Lu Chaojing Tian Bo Xin Lei Lin Han Zhang Yanhui Zhang Xun Zhou Siwei Wan Kangkang Zhou Jun Li Zhaoshen Chen Hezhong Wang Luowei Yan Bian;Ye Gao;Chaojing Lu;Bo Tian;Lei Xin;Han Lin;Yanhui Zhang;Xun Zhang;Siwei Zhou;Kangkang Wan;Jun Zhou;Zhaoshen Li;Hezhong Chen;Luowei Wang

作者机构：Department of Gastroenterology Changhai Hospital Naval Medical University Shanghai China Department of Thoracic Surgery Changhai Hospital Naval Medical University Shanghai China Wuhan Ammunition Life-tech Co. Ltd. Wuhan Hubei China 

出 版 物：《中华医学杂志(英文版)》 (Chinese Medical Journal)

年 卷 期：2024年第137卷第14期

页      面：1724-1735页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：This research was supported by the Science and Technology Commission of Shanghai Municipality(No. 21Y31900100) 

主　　题：Esophageal squamous cell carcinoma Cell-free DNA DNA methylation landscape Biomarker Liquid biopsy Early detection 

摘      要：Background: Early detection of esophageal squamous cell carcinoma (ESCC) can considerably improve the prognosis of patients. Aberrant cell-free DNA (cfDNA) methylation signatures are a promising tool for detecting ESCC. However, available markers based on cell-free DNA methylation are still inadequate. This study aimed to identify ESCC-specific cfDNA methylation markers and evaluate the diagnostic performance in the early detection of ***: We performed whole-genome bisulfite sequencing (WGBS) for 24 ESCC tissues and their normal adjacent tissues. Based on the WGBS data, we identified 21,469,837 eligible CpG sites (CpGs). By integrating several methylation datasets, we identified several promising ESCC-specific cell-free DNA methylation markers. Finally, we developed a dual-marker panel based on methylatedKCNA3 andOTOP2, and then, we evaluated its performance in our training and validation ***: The ESCC diagnostic model constructed based onKCNA3 andOTOP2 had an AUC of 0.91 [95% CI: 0.85–0.95], and an optimal sensitivity and specificity of 84.91% and 94.32%, respectively, in the training cohort. In the independent validation cohort, the AUC was 0.88 [95% CI: 0.83–0.92], along with an optimal sensitivity of 81.5% and specificity of 92.9%. The model sensitivity for stage I–II ESCC was 78.4%, which was slightly lower than the sensitivity of the model (85.7%) for stage III–IV ***: The dual-target panel based on cfDNA showed excellent performance for detecting ESCC and might be an alternative strategy for screening ESCC.