NCT07224737

Liquid Biopsy Using Exosomal miRNA Enables Risk Stratification of Potential Metastasis in Patients With Intrahepatic Cholangiocarcinoma.

Machine Learning-based Exosome Liquid Biopsy Enables Stratification of Occult Metastasis Risk in Patients With Intrahepatic Cholangiocarcinoma

• Status: Completed
• Phase: —
• Study type: Observational
• Enrollment: 230 (actual)
• Sponsor: City of Hope Medical Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Occult metastasis at the time of surgery is a major driver of poor outcomes in intrahepatic cholangiocarcinoma (ICC), yet reliable preoperative biomarkers to identify such patients are lacking. The EXOMIC study aims to develop and validate a circulating exosomal microRNA (exo-miRNA)-based liquid biopsy assay to detect occult metastasis preoperatively in patients with resectable ICC.

Detailed description

Intrahepatic cholangiocarcinoma (ICC) incidence is rising globally, and prognosis remains poor. Patients harboring occult micrometastases that are not detected on preoperative imaging often experience rapid recurrence and significantly worse survival. Tumor-derived exosomes contribute to pre-metastatic niche formation and carry microRNAs that reflect aggressive metastatic potential. Circulating exosomal microRNA profiles may serve as non-invasive biomarkers to reveal occult metastasis before surgery. Preoperative exosomes will be analyzed using small RNA sequencing (discovery) followed by RT-qPCR validation and machine-learning modeling to develop a predictive score for occult metastasis. The study will evaluate diagnostic performance (sensitivity, specificity, accuracy, AUROC), prognostic relevance (OS/RFS), and clinical utility (decision curve analysis) to establish a biologically informed framework for treatment stratification in ICC.

Conditions

• Intrahepatic Cholangiocarcinoma (Icc)

Interventions

Type	Name	Description
DIAGNOSTIC_TEST	EXOMIC small RNA sequencing	High-throughput small RNA sequencing performed on preoperative serum or plasma samples from patients with intrahepatic cholangiocarcinoma (ICC) to identify exosome-derived microRNAs associated with occult metastasis at the time of surgery. Sequencing data were analyzed to detect differentially expressed miRNAs between patients with and without occult metastasis in the discovery cohort.
DIAGNOSTIC_TEST	EXOMIC assay (qRT-PCR validation)	Quantitative reverse transcription PCR (qRT-PCR)-based validation of candidate exosomal microRNAs identified through small RNA sequencing. This assay was performed on preoperative serum or plasma samples from independent ICC patient cohorts to validate the predictive value of selected miRNAs for occult metastasis detection prior to surgical resection.

Timeline

• Start date: 2024-06-21
• Primary completion: 2026-01-18
• Completion: 2026-02-18
• First posted: 2025-11-05
• Last updated: 2026-03-13

Locations

1 site across 1 country: United States