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

NCT07266363 | Recruiting

• 1 other identifier: 23228/SYNERGY
• Study Type: observational
• Target: 600
• Locations: 1 country
• Sites: 1

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.

Conditions

ESCC

Keywords

Exosomal miRNAs; Cell-free miRNAs; Esophageal squamous cell carcinoma; Liquid biopsy

Outcome Measures

Primary Outcomes (1)

• Sensitivity

  Comparison of Pathological Diagnosis and the SYNERGY Assay

  At study completion, an average of one year

Secondary Outcomes (2)

• AUC

  At Study completion, an average of one year

• Specificity

  Time Frame: At study completion, , an average of one year

Study Arms (6)

Discovery cohort (ESCC)

Patients with ESCC

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

Discovery cohort (NDC)

Non-Disease Control

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

Training cohort (ESCC)

Patients with ESCC

Diagnostic Test: PCR-based validation (SYNERGY assay)

Training cohort (NDC)

Non-Disease Control

Diagnostic Test: PCR-based validation (SYNERGY assay)

Testing cohort (ESCC)

Patients with ESCC

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

Testing cohort (NDC)

Non-Disease Control

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

Interventions

RT-qPCR quantification of cf- and exo-miRNAs (SYNERGY assay) DIAGNOSTIC_TEST

RT-qPCR quantification of cf- and exo-miRNAs, and construction of machine learning classifier

Testing cohort (ESCC); Testing cohort (NDC)

PCR-based validation (SYNERGY assay) DIAGNOSTIC_TEST

PCR-based validation of the SYNERGY miRNA panel

Training cohort (ESCC); Training cohort (NDC)

Small RNA sequencing of exo- and cf-miRNAs DIAGNOSTIC_TEST

Identification of differentially expressed cf-miRNAs

Discovery cohort (ESCC); Discovery cohort (NDC)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with histologically confirmed ESCC Healthy volunteers or non-disease controls (NDC)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• City of Hope Medical Center: lead

Study Sites (1)

City of Hope Medical Center

Monrovia, California, 91016, United States

RECRUITING

Related Publications (11)

• Mao Y, Fu Z, Zhang Y, Dong L, Zhang Y, Zhang Q, Li X, Wang C. A six-microRNA risk score model predicts prognosis in esophageal squamous cell carcinoma. J Cell Physiol. 2019 May;234(5):6810-6819. doi: 10.1002/jcp.27429. Epub 2018 Nov 1.

  PMID: 30387125 BACKGROUND

• Li T, Sun G, Ye H, Song C, Shen Y, Cheng Y, Zou Y, Fang Z, Shi J, Wang K, Dai L, Wang P. ESCCPred: a machine learning model for diagnostic prediction of early esophageal squamous cell carcinoma using autoantibody profiles. Br J Cancer. 2024 Sep;131(5):883-894. doi: 10.1038/s41416-024-02781-w. Epub 2024 Jul 2.

  PMID: 38956246 BACKGROUND

• Li K, Lin Y, Zhou Y, Xiong X, Wang L, Li J, Zhou F, Guo Y, Chen S, Chen Y, Tang H, Qiu X, Cai S, Zhang D, Bremer E, Jim Yeung SC, Zhang H. Salivary Extracellular MicroRNAs for Early Detection and Prognostication of Esophageal Cancer: A Clinical Study. Gastroenterology. 2023 Oct;165(4):932-945.e9. doi: 10.1053/j.gastro.2023.06.021. Epub 2023 Jul 1.

  PMID: 37399999 BACKGROUND

• Miyoshi J, Zhu Z, Luo A, Toden S, Zhou X, Izumi D, Kanda M, Takayama T, Parker IM, Wang M, Gao F, Zaidi AH, Baba H, Kodera Y, Cui Y, Wang X, Liu Z, Goel A. A microRNA-based liquid biopsy signature for the early detection of esophageal squamous cell carcinoma: a retrospective, prospective and multicenter study. Mol Cancer. 2022 Feb 11;21(1):44. doi: 10.1186/s12943-022-01507-x.

  PMID: 35148754 BACKGROUND

• Chen J, Zheng Y, Wang Z, Gao Q, Hao K, Chen X, Ke N, Lv X, Weng J, Zhong Y, Huang Z, Fu M, Zhao L, Lin F, Mi H, Tang H, Yu C, Huang Y. Development a glycosylated extracellular vesicle-derived miRNA Signature for early detection of esophageal squamous cell carcinoma. BMC Med. 2025 Jan 23;23(1):39. doi: 10.1186/s12916-025-03871-z.

  PMID: 39849483 BACKGROUND

• Codipilly DC, Wang KK. Squamous Cell Carcinoma of the Esophagus. Gastroenterol Clin North Am. 2022 Sep;51(3):457-484. doi: 10.1016/j.gtc.2022.06.005. Epub 2022 Aug 29.

  PMID: 36153105 BACKGROUND

• Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011 Mar-Apr;61(2):69-90. doi: 10.3322/caac.20107. Epub 2011 Feb 4.

  PMID: 21296855 BACKGROUND

• Codipilly DC, Qin Y, Dawsey SM, Kisiel J, Topazian M, Ahlquist D, Iyer PG. Screening for esophageal squamous cell carcinoma: recent advances. Gastrointest Endosc. 2018 Sep;88(3):413-426. doi: 10.1016/j.gie.2018.04.2352. Epub 2018 Apr 27.

  PMID: 29709526 BACKGROUND

• Chen J, Liu X, Zhang Z, Su R, Geng Y, Guo Y, Zhang Y, Su M. Early Diagnostic Markers for Esophageal Squamous Cell Carcinoma: Copy Number Alteration Gene Identification and cfDNA Detection. Lab Invest. 2024 Oct;104(10):102127. doi: 10.1016/j.labinv.2024.102127. Epub 2024 Aug 23.

  PMID: 39182610 BACKGROUND

• Ma L, Dou L, Liu Y, Zhang Y, Liu X, Ng HL, Chu J, Liu Y, Li Z, Ke Y, Liu S, He S, Wang G. Development and validation of predictive models combining cell-Free DNA motifs and protein biomarkers for early detection of esophageal squamous cell carcinoma and precancerous lesion. Biomark Res. 2025 Oct 14;13(1):126. doi: 10.1186/s40364-025-00840-9.

  PMID: 41088482 BACKGROUND

• Zheng Y, Xing W, BingWei, Liu X, Liang G, Yuan D, Yang K, Wang W, Chen D, Ma J. Detection of a novel DNA methylation marker panel for esophageal cancer diagnosis using circulating tumor DNA. BMC Cancer. 2024 Dec 26;24(1):1578. doi: 10.1186/s12885-024-13301-7.

  PMID: 39725880 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

RNA from plasma or serum

MeSH Terms

Conditions

Esophageal Squamous Cell Carcinoma

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Esophageal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Study Officials

• Ajay Goel, PhD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ajay Goel, PhD

CONTACT

626-218-3452; ajgoel@coh.org

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 18, 2025
• First Posted: December 5, 2025
• Study Start: January 15, 2025
• Primary Completion (Estimated): June 18, 2026
• Study Completion (Estimated): June 18, 2026
• Last Updated: December 5, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)