首页|Novel DNA methylation markers for early detection of gastric cardia adenocarcinoma and esophageal squamous cell carcino-ma

Novel DNA methylation markers for early detection of gastric cardia adenocarcinoma and esophageal squamous cell carcino-ma

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Gastric cardia adenocarcinoma(GCA)and esophageal squamous cell carcinoma(ESCC)present significant health challenges in China,often diagnosed at advanced stages with poor prognoses.However,effective biomarkers for early detection remain elusive.This study aimed to integrate methylome and transcriptome data to identify DNA methylation markers for the early detection of GCA and ESCC.In the discovery stage,we conducted Infinium MethylationEPIC array analysis on 36 paired GCA and non-tumor adjacent tissues(NAT),identifying dif-ferentially methylated CpG sites(DMCs)between GCA/ESCC and NAT through combined analyses of in-house and publicly available data.In the validation stage,targeted pyrosequencing and quantitative real-time RT-PCR were performed on paired tumor and NAT samples from 50 GCA and 50 ESCC patients.In the application stage,an independent set of 438 samples,including GCA,ESCC,high-and low-grade dysplasia(HGD/LGD),and normal controls,was tested for selected DMCs using pyrosequencing.Our analysis validated three GCA-specific,two ESCC-specific,and one tumor-shared DMCs,exhibiting significant hypermethylation and decreased expression of target genes in tumor samples compared with NAT.Leveraging these DMCs,we developed a GCA-specific 4-marker panel(cg27284428,cg11798358,cg07880787,and cg00585116)with an area under the receiver operating characteristic curve(AUC)of 0.917,effectively distinguishing between cardia HGD/GCA patients and cardia LGD/normal controls.Similarly,an ESCC-specific 3-marker panel(cg14633892,cg04415798,and cg00585116)achieved an AUC of 0.865 in distinguishing esophageal HGD/ESCC cases.Furthermore,integrating cg00585116,age,and alcohol con-sumption yielded a tumor-shared logistic model with good discrimination for two cancer/HGD(AUC,0.767;95%confidence interval,0.720-0.813).The mean AUC of the model after 5-fold cross-validation was 0.764.In summary,our study identifies novel DNA methylation markers capable of accurately distinguishing GCA/ESCC and HGD from LGD and normal controls.These findings offer promising prospects for targeted DNA methylation assays in future minimally invasive cancer screening methods.

gastric cardia adenocarcinomaesophageal squamous cell carcinomahigh-grade dysplasiaDNA methylation markersearly detection

Zhiyuan Fan、Jiajie Hao、Feifan He、Hao Jiang、Jinwu Wang、Minjuan Li、Xinqing Li、Ru Chen、Wenqiang Wei

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Office of National Central Cancer Registry,National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100021,China

State Key Laboratory of Molecular Oncology,Center for Cancer Precision Medicine,National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100021,China

School of Population Medicine and Public Health,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100730,China

Department of Pathology,Linzhou Cancer Hospital,Linzhou 456550,China

Department of Orthopedic Surgery,Beijing Jishuitan Hospital,Capital Medical University,Beijing 100035,China

Collaborative Innovation Center for Cancer Personalized Medicine,Nanjing Medical University,Nanjing 211166,China

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2024

中国科学:生命科学(英文版)
中国科学院

中国科学:生命科学(英文版)

CSTPCD
影响因子:0.806
ISSN:1674-7305
年,卷(期):2024.67(12)