Prognostic Value of Circulating Exosomal DNA in Esophageal Squamous Cell Carcinoma: A Prospective Cohort Study

Ann Surg Oncol. 2026 Aug;33(8):7688-7698. doi: 10.1245/s10434-026-19757-0. Epub 2026 May 11.

Abstract

Background: Reliable biomarkers for prognostication and recurrence surveillance in esophageal squamous cell carcinoma (ESCC) remain limited. The authors therefore investigated the potential clinical utility of exosomal DNA, which has emerged as a promising component of liquid biopsy.

Methods: This study screened 54 patients with ESCC. After exclusions, 210 blood samples from 21 patients underwent mutation-specific droplet digital polymerase chain reaction assays of plasma exosomal DNA (exoDNA) and circulating tumor DNA (ctDNA) before and after treatment. Kaplan-Meier and receiver operating characteristic analyses were performed to examine associations with overall survival (OS), disease-specific survival (DSS), relapse-free survival (RFS), and recurrence.

Results: Pretreatment exoDNA positivity was significantly associated with shorter DSS (p = 0.035) and shorter RFS (p = 0.048). Post-treatment exoDNA positivity was significantly associated with shorter OS (p = 0.0008), DSS (p = 0.0001), and RFS (p = 0.0001). Post-treatment ctDNA positivity was associated with shorter DSS (p = 0.038).

Conclusions: In ESCC, exoDNA demonstrated prognostic and predictive value, supporting its potential role as a complementary biomarker for postoperative surveillance.

Keywords: Biomarker; Circulating tumor DNA; Esophageal squamous cell carcinoma; Exosomal DNA; Recurrence prediction.

MeSH terms

  • Aged
  • Biomarkers, Tumor* / blood
  • Biomarkers, Tumor* / genetics
  • Circulating Tumor DNA* / blood
  • Circulating Tumor DNA* / genetics
  • Esophageal Neoplasms* / blood
  • Esophageal Neoplasms* / genetics
  • Esophageal Neoplasms* / pathology
  • Esophageal Neoplasms* / therapy
  • Esophageal Squamous Cell Carcinoma* / blood
  • Esophageal Squamous Cell Carcinoma* / genetics
  • Esophageal Squamous Cell Carcinoma* / pathology
  • Exosomes* / genetics
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local* / blood
  • Neoplasm Recurrence, Local* / genetics
  • Neoplasm Recurrence, Local* / pathology
  • Prognosis
  • Prospective Studies
  • Survival Rate

Substances

  • Biomarkers, Tumor
  • Circulating Tumor DNA