Genomic characterization and risk stratification of esophageal squamous dysplasia

Objectives:The majority of esophageal squamous dysplasia(ESD)patients progress slowly,while a subset of patients can undergo recurrence rapidly or progress to invasive cancer even after proper treatment.However,the molecular mechanisms underlying these clinical observations are still largely unknown.Methods:By sequencing the genomic data of 160 clinical samples from 49 tumor-free ESD patients and 88 esophageal squamous cell carcinoma(ESCC)patients,we demonstrated lower somatic mutation and copy number alteration(CNA)burden in ESD compared with ESCC.Results:Cross-species screening and functional assays identified ACSM5 as a novel driver gene for ESD progression.Furthermore,we revealed that miR-4292 promoted ESD progression and could serve as a non-invasive diagnostic marker for ESD.Conclusions:These findings largely expanded our understanding of ESD genetics and tumorigenesis,which possessed promising significance for improving early diagnosis,reducing overtreatment,and identifying high-risk ESD patients.