Tai Derek, Latif Kareem, Shah Pranati, Park Daniel, Crook Christiana, Guzman Sofia, Brar Gagandeep, Li Daneng, Castillo Dani
Department of Internal Medicine, Loma Linda University Medical Center, Loma Linda, CA, United States.
Department of Internal Medicine, University of California San Francisco Fresno, Fresno, CA, United States.
Front Oncol. 2025 Aug 14;15:1622984. doi: 10.3389/fonc.2025.1622984. eCollection 2025.
Circulating tumor DNA (ctDNA) has emerged as a promising biomarker for the early detection of esophageal cancer (EC), offering a minimally invasive means to assess tumor-derived genomic and epigenomic alterations. This review synthesizes current data on ctDNA biology, detection technologies, diagnostic performance, and clinical applicability in both esophageal adenocarcinoma and squamous cell carcinoma. We conducted a comprehensive literature review of PubMed-indexed studies on ctDNA in EC, emphasizing recent (January 1, 2019- December 31, 2024) findings, systematic reviews, and meta-analyses. Key data on ctDNA characteristics, diagnostic performance in both early-stage esophageal adenocarcinoma and squamous cell carcinoma, and clinical outcomes were extracted. We also discuss technical and clinical challenges in ctDNA assays and future perspectives for integrating ctDNA evaluation into clinical practice. We highlight technological innovations such as methylation profiling, fragmentomics, and ultrasensitive sequencing, and compare ctDNA-based approaches to alternative non-endoscopic modalities. While early studies report encouraging sensitivity and specificity for ctDNA in high-risk populations, specifically with methylation assays, current data remain limited by small sample sizes, retrospective design, low tumor DNA abundance, and heterogeneity in assay methodology. Furthermore, the clinical implementation of ctDNA-based screening must address population-level feasibility, cost-effectiveness, and health equity. We conclude that ctDNA holds significant potential for early EC detection but remains investigational pending validation in large prospective cohorts.
循环肿瘤DNA（ctDNA）已成为一种很有前景的食管癌（EC）早期检测生物标志物，为评估肿瘤来源的基因组和表观基因组改变提供了一种微创手段。本综述综合了目前关于ctDNA生物学、检测技术、诊断性能以及在食管腺癌和鳞状细胞癌中的临床适用性的数据。我们对PubMed索引的关于EC中ctDNA的研究进行了全面的文献综述，重点关注近期（2019年1月1日至2024年12月31日）的研究结果、系统评价和荟萃分析。提取了关于ctDNA特征、早期食管腺癌和鳞状细胞癌诊断性能以及临床结局的关键数据。我们还讨论了ctDNA检测中的技术和临床挑战，以及将ctDNA评估整合到临床实践中的未来前景。我们强调了甲基化谱分析、片段组学和超灵敏测序等技术创新，并将基于ctDNA的方法与其他非内镜检测方法进行了比较。虽然早期研究报告了ctDNA在高危人群中具有令人鼓舞的敏感性和特异性，特别是甲基化检测，但目前的数据仍然受到样本量小、回顾性设计、肿瘤DNA丰度低以及检测方法异质性的限制。此外，基于ctDNA的筛查的临床应用必须解决人群水平的可行性、成本效益和健康公平性问题。我们得出结论，ctDNA在早期EC检测中具有巨大潜力，但在大型前瞻性队列中进行验证之前仍处于研究阶段。
