Genome-wide methylation profiling identified methylated KCNA3 and OTOP2 as promising diagnostic markers for esophageal squamous cell carcinomaOACSTPCDMEDLINE
Genome-wide methylation profiling identified methylated KCNA3 and OTOP2 as promising diagnostic markers for esophageal squamous cell carcinoma
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 ESCC. Methods: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 methylated KCNA3 and OTOP2,and then,we evaluated its performance in our training and validation cohorts. Results:The ESCC diagnostic model constructed based on KCNA3 and OTOP2 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 stageⅢ-Ⅳ ESCC. Conclusion:The dual-target panel based on cfDNA showed excellent performance for detecting ESCC and might be an alternative strategy for screening ESCC.
Yan Bian;Kangkang Wan;Jun Zhou;Zhaoshen Li;Hezhong Chen;Luowei Wang;Ye Gao;Chaojing Lu;Bo Tian;Lei Xin;Han Lin;Yanhui Zhang;Xun Zhang;Siwei Zhou
Department of Gastroenterology,Changhai Hospital,Naval Medical University,Shanghai 200433,ChinaWuhan Ammunition Life-tech Co.,Ltd.,Wuhan,Hubei 430000,ChinaDepartment of Thoracic Surgery,Changhai Hospital,Naval Medical University,Shanghai 200433,China
Esophageal squamous cell carcinomaCell-free DNADNA methylation landscapeBiomarkerLiquid biopsyEarly detection
《中华医学杂志(英文版)》 2024 (014)
1724-1735 / 12
This research was supported by the Science and Technology Commission of Shanghai Municipality(No.21Y31900100).
评论