ESCC
Conditions
Keywords
Exosomal miRNAs, Cell-free miRNAs, Esophageal squamous cell carcinoma, Liquid biopsy
Brief 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.
Interventions
DIAGNOSTIC_TESTSmall RNA sequencing of exo- and cf-miRNAs
Identification of differentially expressed cf-miRNAs
DIAGNOSTIC_TESTRT-qPCR quantification of cf- and exo-miRNAs (SYNERGY assay)
RT-qPCR quantification of cf- and exo-miRNAs, and construction of machine learning classifier
DIAGNOSTIC_TESTPCR-based validation (SYNERGY assay)
PCR-based validation of the SYNERGY miRNA panel
Sponsors
City of Hope Medical Center
Study design
Observational model
CASE_CONTROL
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sensitivity | At study completion, an average of one year | Comparison of Pathological Diagnosis and the SYNERGY Assay |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUC | At Study completion, an average of one year | AUC of integrated cf- + exo-miRNA model |
| Specificity | Time Frame: At study completion, , an average of one year | Description: Comparison of Pathological Diagnosis and the SYNERGY Assay |
Countries
United States
Contacts
CONTACTAjay Goel, PhD
PRINCIPAL_INVESTIGATORAjay Goel, PhD
City of Hope Medical Center
Outcome results
None listed