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

Purpose

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.

Condition

  • ESCC

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
Yes

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

Study Design

Phase
Study Type
Observational
Observational Model
Case-Control
Time Perspective
Retrospective

Arm Groups

ArmDescriptionAssigned Intervention
Discovery cohort (ESCC) Patients with ESCC
  • Diagnostic Test: Small RNA sequencing of exo- and cf-miRNAs
    Identification of differentially expressed cf-miRNAs
Discovery cohort (NDC) Non-Disease Control
  • Diagnostic Test: Small RNA sequencing of exo- and cf-miRNAs
    Identification of differentially expressed cf-miRNAs
Training cohort (ESCC) Patients with ESCC
  • Diagnostic Test: PCR-based validation (SYNERGY assay)
    PCR-based validation of the SYNERGY miRNA panel
Training cohort (NDC) Non-Disease Control
  • Diagnostic Test: PCR-based validation (SYNERGY assay)
    PCR-based validation of the SYNERGY miRNA panel
Testing cohort (ESCC) Patients with ESCC
  • 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
Testing cohort (NDC) Non-Disease Control
  • 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

Recruiting Locations

City of Hope Medical Center
Monrovia 5374175, California 5332921 91016
Contact:
Ajay Goel, PhD
626-218-3452
ajgoel@coh.org

More Details

Status
Recruiting
Sponsor
City of Hope Medical Center

Study Contact

Ajay Goel, PhD
626-218-3452
ajgoel@coh.org

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.