NCT07266363

Integrated Cf-miRNA and Exosomal miRNA Signature for Early Detection of Esophageal Squamous Cell Carcinoma

SYNERGY Study: Early Detection Through Integrated Evaluation of Cell-Free and Exosomal microRNAs for Biomarker-Guided Screening of Esophageal Squamous Cell Carcinoma

• Status: Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 600 (estimated)
• Sponsor: City of Hope Medical Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Accepted

Summary

Esophageal squamous cell carcinoma (ESCC) remains a highly lethal cancer worldwide, largely due to late diagnosis. Current screening methods such as upper endoscopy are invasive, operator-dependent, and limited in their ability to detect early-stage lesions. To address this clinical need, the SYNERGY study seeks to develop a non-invasive, blood-based biomarker assay that integrates cell-free microRNAs (cf-miRNAs) and exosomal microRNAs (exo-miRNAs) to detect ESCC at an early and potentially curable stage. This multicenter translational study includes discovery, training, and validation phases using preoperative plasma or serum samples. By combining the tumor specificity of exosomal miRNAs with the systemic sensitivity of cf-miRNAs, SYNERGY aims to construct a robust diagnostic model with high sensitivity and specificity for early ESCC detection.

Detailed description

Esophageal cancer is the 11th most common cancer globally and the 7th leading cause of cancer-related death, with an estimated 511,000 new cases and 445,000 deaths annually. ESCC accounts for the majority of cases worldwide. Despite advances in endoscopy and therapy, outcomes for advanced ESCC remain poor, highlighting the pressing need for sensitive, minimally invasive early detection strategies. Exosomal miRNAs (exo-miRNAs) are selectively released by tumor cells and remain stable in circulation, enabling reliable detection of tumor-specific signals. Cell-free miRNAs (cf-miRNAs) circulate broadly and can reflect overall tumor burden, metastatic spread, and microenvironmental changes. Previous ESCC biomarker studies were limited by small validation cohorts and reliance on tissue-based public datasets that do not fully capture circulating biomarker patterns. The SYNERGY study addresses these limitations through comprehensive discovery analysis and multi-cohort blood-based validation.

Conditions

• ESCC

Interventions

Type	Name	Description
DIAGNOSTIC_TEST	Small RNA sequencing of exo- and cf-miRNAs	Identification of differentially expressed cf-miRNAs
DIAGNOSTIC_TEST	RT-qPCR quantification of cf- and exo-miRNAs (SYNERGY assay)	RT-qPCR quantification of cf- and exo-miRNAs, and construction of machine learning classifier
DIAGNOSTIC_TEST	PCR-based validation (SYNERGY assay)	PCR-based validation of the SYNERGY miRNA panel

Timeline

• Start date: 2025-01-15
• Primary completion: 2026-06-18
• Completion: 2026-06-18
• First posted: 2025-12-05
• Last updated: 2025-12-05

Locations

1 site across 1 country: United States