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

City of Hope

Status: Enrolling

Conditions: ESCC

Treatments: Diagnostic Test: Small RNA sequencing of exo- and cf-miRNAs; Diagnostic Test: RT-qPCR quantification of cf- and exo-miRNAs (SYNERGY assay); Diagnostic Test: PCR-based validation (SYNERGY assay)

Study type: Observational

Funder types: Other

Identifiers

NCT07266363

23228/SYNERGY

Details and patient eligibility

About

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.

Full 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.

Enrollment: 600 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Adults age 18 to 90 years
• Histologically confirmed esophageal squamous cell carcinoma
• No prior systemic therapy before sample collection
• For control groups: absence of malignant disease

Exclusion criteria

• Lack of informed consent
• Inadequate sample volume or RNA quality
• Prior cancer within 5 years (except localized cancers)
• Active systemic inflammation that may alter circulating RNA profiles

Trial design

600 participants in 6 patient groups

Discovery cohort (ESCC)

Description:

Patients with ESCC

Treatment:

Diagnostic Test: Small RNA sequencing of exo- and cf-miRNAs

Discovery cohort (NDC)

Description:

Non-Disease Control

Treatment:

Diagnostic Test: Small RNA sequencing of exo- and cf-miRNAs

Training cohort (ESCC)

Description:

Patients with ESCC

Treatment:

Diagnostic Test: PCR-based validation (SYNERGY assay)

Training cohort (NDC)

Description:

Non-Disease Control

Treatment:

Diagnostic Test: PCR-based validation (SYNERGY assay)

Testing cohort (ESCC)

Description:

Patients with ESCC

Treatment:

Diagnostic Test: RT-qPCR quantification of cf- and exo-miRNAs (SYNERGY assay)

Testing cohort (NDC)

Description:

Non-Disease Control

Treatment:

Diagnostic Test: RT-qPCR quantification of cf- and exo-miRNAs (SYNERGY assay)