Genomic characterization and risk stratification of esophageal squamous dysplasia

• DOI: 10.1515/mr-2024-0008
• Publication Date: 2024-05-14T11:13:12Z
• Authors: Qingjie Min; Min Zhang; Dongmei Lin; Weimin Zhang; Xianfeng Li; Lianmei Zhao; Huajing Teng; Tao He; Wei Sun; Jiawen Fan; Xiying Yu; Jie Chen; Jinting Li; Xiaohan Gao; Bin Dong; Rui Liu; Xuefeng Liu; Yongmei Song; Yongping Cui; Shih-Hsin Lu; Ruiqiang Li; Mingzhou Guo; Yan Wang; Qimin Zhan
• Keywords: 0301 basic medicine; Genomic alteration; acsm5; Medizin; R; 610; esophageal squamous dysplasia; Early diagnosis; mir-4292; MiR-4292; ACSM5; 03 medical and health sciences; Sonstiges; Esophageal squamous dysplasia; Medicine; Original Article; genomic alteration; early diagnosis

Abstract

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.