Detection of Minimal Residual Disease Using Exosomal miRNA Distant Metastasis Markers (ENLIGHT)

City of Hope

Status: Enrolling

Conditions: Gastric Cancer

Treatments: Diagnostic Test: ENLIGHT Assay; Diagnostic Test: small RNA-seq or array

Study type: Observational

Funder types: Other

Identifiers

NCT07243015

23228/ENLIGHT

Details and patient eligibility

About

Gastric cancer (GC) is a leading cause of cancer-related death worldwide. Even in patients undergoing curative surgery for non-metastatic disease, postoperative recurrence frequently occurs due to undetected minimal residual disease (MRD). This study aims to establish a highly sensitive and specific liquid biopsy assay using exosomal microRNAs (exo-miRNAs) to detect MRD and predict distant metastasis before clinical recurrence.

Full description

Postoperative recurrence in gastric cancer is largely driven by occult micrometastatic disease that remains undetectable by conventional imaging. While circulating tumor DNA (ctDNA) assays have shown utility in MRD detection, their limited sensitivity and tumor-type variability hinder consistent application in gastric cancer.

Exosomal microRNAs (exo-miRNAs), encapsulated within lipid bilayer vesicles, remain stable in circulation and reflect tumor-derived molecular information. This study seeks to develop and validate an exosomal miRNA-based signature capable of detecting minimal residual disease and predicting future distant metastasis after curative gastrectomy.

Study Phases

1. Discovery Phase - Comprehensive small RNA sequencing to identify miRNAs specific to distant metastasis in gastric cancer.
2. Training Phase - RT-qPCR-based quantification of candidate exo-miRNAs in postoperative plasma samples to develop an MRD signature.
3. Validation Phase - Independent cohort testing to evaluate the diagnostic performance, sensitivity, and specificity of the exosomal MRD panel.

Ultimately, the ENLIGHT assay aims to guide postoperative adjuvant chemotherapy by stratifying patients according to MRD status, enabling precision surveillance and early intervention.

Enrollment: 500 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Histologically confirmed gastric adenocarcinoma.
• Underwent curative-intent resection (R0).
• Availability of pre- and postoperative plasma samples.
• Documented clinical follow-up data (recurrence/metastasis status).
• Provided written informed consent.

Exclusion criteria

• Insufficient plasma volume or RNA quality for exosomal extraction.
• Presence of synchronous or metachronous malignancies.
• Received neoadjuvant chemotherapy without postoperative follow-up.
• Lack of consent or incomplete clinicopathologic data.

Trial design

500 participants in 6 patient groups

Discovery Cohort - Distant Metastasis Positive

Description:

Patients with postoperative distant metastasis; used for biomarker discovery via small RNA sequencing.

Treatment:

Diagnostic Test: small RNA-seq or array

Discovery Cohort - Distant Metastasis Negative

Description:

Patients without postoperative metastasis; used as reference controls in discovery phase.

Treatment:

Diagnostic Test: small RNA-seq or array

Training Cohort - MRD Positive (High Risk)

Description:

Patients exhibiting postoperative recurrence within 12 months.

Treatment:

Diagnostic Test: ENLIGHT Assay

Training Cohort - MRD Negative (Low Risk)

Description:

Patients without recurrence ≥12 months postoperatively.

Treatment:

Diagnostic Test: ENLIGHT Assay

Validation Cohort - MRD Positive

Description:

Independent validation cohort with confirmed distant metastasis or MRD positivity.

Treatment:

Diagnostic Test: ENLIGHT Assay

Validation Cohort - MRD Negative

Description:

Independent validation cohort without recurrence/metastasis.

Treatment:

Diagnostic Test: ENLIGHT Assay