Evidence map›Paper›PMID 40817602›Full record

ArticleClinical and translational medicine2025

Gene-specific ctDNA dynamics predict tumour burden and survival outcomes in ESCC: A prospective cohort study.

Rentong Gu, Tao Liu, Wen Cheng, Mengxing Li, Xiaowei Wang, Hai Jin

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Article in Clinical and translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

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4citing papers in PubMed
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1 · What the graph read from it

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4 citing papers in PubMed.

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5 · Who and what money

Authors and funding

6 authors.

Rentong GuDepartment of Thoracic Surgery, Changhai Hospital, Naval Medical University, Shanghai, China.
Tao LiuDepartment of Thoracic Surgery, Peking University First Hospital, Beijing, China.
Wen ChengDepartment of Thoracic Surgery, Changhai Hospital, Naval Medical University, Shanghai, China.
Mengxing LiDepartment of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
Xiaowei WangDepartment of Thoracic Surgery, Changhai Hospital, Naval Medical University, Shanghai, China.
Hai JinDepartment of Thoracic Surgery, Changhai Hospital, Naval Medical University, Shanghai, China.ORCID 0000-0003-0430-2834

Funding

National Natural Science Foundation of China 81672890Science and Technology Commission of Shanghai Municipality 15411951700
6 · The paper itself

Abstract

backgroundOesophageal squamous cell carcinoma (ESCC) remains a highly aggressive malignancy with limited biomarkers for monitoring tumour burden and prognosis. Circulating tumour DNA (ctDNA) has emerged as a promising tool for real-time disease assessment, but its clinical utility in ESCC remains underexplored.

methodsIn this prospective cohort study, we analysed preoperative and postoperative ctDNA from 54 treatment-naïve ESCC patients undergoing radical surgery using a 61-gene panel. Associations between ctDNA mutations, clinicopathological characteristics and survival outcomes were evaluated.

resultsPreoperative ctDNA mutations were detected in 96.3% of patients (52/54), with Tumour Protein 53 (TP53) (59.3%), Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) (31.5%) and Phosphatase and Tensin Homologue (PTEN) (13.0%) being most prevalent. Surgical resection significantly reduced ctDNA positivity (p < .0001). Advanced-stage tumours exhibited higher frequencies of PIK3CA (47.8% vs. 19.4%, p = .026) and PTEN mutations (26.1% vs. 3.2%, p = .034). Survival analysis revealed that postoperative TP53 ctDNA positivity predicted worse disease-free survival (DFS; Hazard Ratio (HR) = 3.64, p = .005) and overall survival (OS; HR = 3.29, p = .009), while PIK3CA positivity was associated with improved OS (p = .032). Strikingly, preoperative PTEN ctDNA-positive patients showed dramatically worse outcomes, with median DFS of 4.01 versus 33.27 months (HR = 7.53, p < .001) and OS of 11.80 versus 45.17 months (HR = 5.35, p < .001). In multivariate analysis, preoperative PTEN positivity remained the strongest independent prognostic factor for both DFS (HR = 7.28, p = .002) and OS (HR = 3.76, p = .028), surpassing Tumour, Node, Metastasis (TNM) stage.

conclusionsOur findings highlight the dynamic role of ctDNA in reflecting ESCC tumour burden and prognosis. While tumour-agnostic ctDNA analysis showed limited clinical utility, gene-specific mutations (TP53, PIK3CA and PTEN) demonstrated significant prognostic value. Preoperative PTEN ctDNA positivity emerged as a robust predictor of aggressive disease, suggesting its potential for risk stratification and personalised therapeutic strategies in ESCC.

Indexed as

Circulating Tumor DNAEsophageal NeoplasmsEsophageal Squamous Cell CarcinomaTumor BurdenAdultAgedBiomarkers, TumorClass I Phosphatidylinositol 3-KinasesFemaleHumansMaleMiddle AgedMutationPrognosisProspective StudiesPTEN PhosphohydrolaseBiomarkers, TumorCirculating Tumor DNAClass I Phosphatidylinositol 3-KinasesPTEN Phosphohydrolasecirculating tumour DNA (ctDNA)oesophageal squamous cell carcinoma (ESCC)PIK3CAprognosisPTENTP53

Identifiers

PMID40817602
PMCPMC12356824

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