Application progress and clinical value of circulating tumor DNA detection technologies in monitoring minimal residual disease in esophageal cancer_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

SUN Xintian ^1,2,3,4 ,  ZHU Xiaokang ^1,2 , ZHOU Sixiang ^3,4 , DENG Qi ^3,4 , ZHANG An ^3,4 , HU Zhicheng ^3,4 , MIN Weirun ^2,3 ,  GOU Yunjiu ^3,4 , ZHU Gongjian ¹ , LI Yanlong ²

1. Department of Thoracic Surgery, Gansu Hospital of Sun Yat-sen University Cancer Center (Gansu Cancer Hospital), Lanzhou, 730000, P. R. China;
2. Department of Cardiothoracic Surgery, Gansu Provincial Hospital of Traditional Chinese Medicine, Lanzhou, 730000, P. R. China;
3. The First Clinical Medical College, Gansu University of Chinese Medicine, Lanzhou, 730000, P. R. China;
4. Department of Thoracic Surgery, Gansu Provincial Hospital, Lanzhou, 730000, P. R. China;

Corresponding?author：

ZHU Xiaokang, Email: 362694313@qq.com; GOU Yunjiu, Email: gouyunjiu@163.com

Keywords：

Esophageal neoplasms; circulating tumor DNA; minimal residual disease; liquid biopsy; molecular diagnostic techniques; treatment monitoring; prognosis

DOI：

10.7507/1007-4848.202512046

Video：

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As a core biomarker of non-invasive liquid biopsy, circulating tumor DNA (ctDNA) provides a breakthrough approach for minimal residual disease (MRD) monitoring in esophageal cancer. Esophageal cancer is clinically characterized by strong invasiveness, high postoperative recurrence rate, and poor prognosis. Traditional imaging and histopathological examinations are difficult to meet the clinical demand for accurate MRD identification due to limitations such as insufficient sensitivity and high invasiveness. This paper systematically reviews the biological basis and technical advances of ctDNA detection, focusing on the advantages and clinical application scenarios of core technologies including digital polymerase chain reaction, next-generation sequencing, and methylation detection. It further analyzes the core clinical value of ctDNA in esophageal cancer MRD monitoring, covering key directions such as early recurrence warning, dynamic evaluation of treatment efficacy, and optimization of individualized treatment strategies. Meanwhile, the main challenges currently faced, including insufficient technical standardization, interference from tumor heterogeneity, and lag in clinical translation, are discussed, and future development trends such as multi-omics integration and artificial intelligence-assisted diagnosis are prospected. This review aims to provide an academic reference for the precise clinical management of esophageal cancer MRD, promote the standardized application and translation of ctDNA technology in clinical practice of cardiothoracic surgery, and ultimately improve the survival prognosis of patients.

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17. Saha S, Araf Y, Promon SK. Circulating tumor DNA in cancer diagnosis, monitoring, and prognosis. J Egypt Natl Canc Inst, 2022, 34(1): 8.
18. Lee J, Cho JH, Lee S, et al. Evaluating the prognostic value of a pan-cancer circulating tumor DNA next-generation sequencing panel in advanced cancer patients. Onco Targets Ther, 2025, 18: 1179-1188.
19. Liu Y, Liu YY, Wang YY, et al. Increased detection of circulating tumor DNA by short fragment enrichment. Transl Lung Cancer Res, 2021, 10(3): 1501-1511.
20. Boniface C, Deig C, Halsey C, et al. The feasibility of patient-specific circulating tumor DNA monitoring throughout multi-modality therapy for locally advanced esophageal and rectal cancer: a potential biomarker for early detection of subclinical disease. Diagnostics (Basel), 2021, 11(1): 73.
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23. Li XX, Liu T, Bacchiocchi A, et al. Ultra-sensitive molecular residual disease detection through whole genome sequencing with single-read error correction. EMBO Mol Med, 2024, 16(9): 2188-2209.
24. Illana FJ, Fernández-Galán E, Mu?oz-Bravo JL, et al. Circulating tumor DNA in patients with cancer: insights from clinical laboratory. Adv Lab Med, 2025, 6(3): 259-276.
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26. Zhou SX, Yin H, Yan L, et al. ctDNA methylation profiling reveals NBL1 as a promising biomarker for early ovarian cancer screening. World J Surg Oncol, 2025, 23(1): 305.
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29. Salta S, Macedo-Silva C, Miranda-Gon?alves V, et al. A DNA methylation-based test for esophageal cancer detection. Biomark Res, 2020, 8(1): 68.
30. Shen JF, Ren YQ, Mao ZY, et al. Improved circulating tumor DNA identification for detection of esophageal squamous cell carcinoma by enzymatic methyl sequencing and hybrid neural network. Sci Rep, 2025, 15(1): 33004.
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41. Matsui H, Eguchi H, Okazaki Y, et al. Comparison of somatic mutations in primary squamous cell carcinomas of the hypopharynx and the esophagus developed in individual patients. Head Neck, 2025, 47(11): 3028-3038.
42. Cai J, Jiang HH, Li SQ, et al. The landscape of actionable genomic alterations by next-generation sequencing in tumor tissue versus circulating tumor DNA in Chinese patients with non-small cell lung cancer. Front Oncol, 2022, 11: 751106.
43. Erkizan HV, Sukhadia S, Natarajan TG, et al. Exome sequencing identifies novel somatic variants in African American esophageal squamous cell carcinoma. Sci Rep, 2021, 11(1): 14814.
44. Chidambaram S, Markar SR. Clinical utility and applicability of circulating tumor DNA testing in esophageal cancer: a systematic review and meta-analysis. Dis Esophagus, 2022, 35(2): doab046.
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Latest ArticlesApplication progress and clinical value of circulating tumor DNA detection technologies in monitoring minimal residual disease in esophageal cancer

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