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

City of Hope

Status: Enrolling

Conditions: Intrahepatic Cholangiocarcinoma (Icc)

Treatments: Diagnostic Test: EXOMIC assay (qRT-PCR validation); Diagnostic Test: EXOMIC small RNA sequencing

Study type: Observational

Funder types: Other

Identifiers

NCT07224737

23228/EXOMIC

Details and patient eligibility

About

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.

Full 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.

Enrollment: 250 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Histologically confirmed ICC (clinical stage I-III).
• Undergoing curative-intent hepatectomy.
• Availability of preoperative pasma or serum sample (≥200 µL).
• Standard staging imaging completed per institutional protocol.
• Written informed consent.

Exclusion criteria

• Extrahepatic cholangiocarcinoma or gallbladder cancer.
• Synchronous non-ICC malignancy.
• Inadequate clinical follow-up.
• Inability to consent.

Trial design

250 participants in 6 patient groups

Training Cohort - ICC with Occult Metastasis

Description:

The cohort of ICC patients who had occult metastasis detected at the time of surgery. Preoperative samples were analyzed using the EXOMIC qRT-PCR assay to validate candidate exosomal microRNAs identified in the discovery cohort.

Treatment:

Diagnostic Test: EXOMIC assay (qRT-PCR validation)

Training Cohort - ICC without Occult Metastasis

Description:

The cohort of ICC patients without occult metastasis at the time of surgery. Preoperative samples were analyzed with the EXOMIC qRT-PCR assay to evaluate differential miRNA expression and refine the predictive model for occult metastasis detection.

Treatment:

Diagnostic Test: EXOMIC assay (qRT-PCR validation)

Validation Cohort - ICC with Occult Metastasis

Description:

The cohort of ICC patients with occult metastasis at the time of primary tumor resection. The EXOMIC qRT-PCR assay was applied to confirm the predictive value of the exosomal miRNA panel in identifying occult metastasis prior to surgery.

Treatment:

Diagnostic Test: EXOMIC assay (qRT-PCR validation)

Validation Cohort - ICC without Occult Metastasis

Description:

The cohort of ICC patients without occult metastasis at the time of surgery. Preoperative samples were analyzed with the EXOMIC qRT-PCR assay to evaluate differential miRNA expression and refine the predictive model for occult metastasis detection.

Treatment:

Diagnostic Test: EXOMIC assay (qRT-PCR validation)

Discovery Cohort - ICC with Occult Metastasis

Description:

Patients with intrahepatic cholangiocarcinoma (ICC) who were found to have occult metastasis at the time of primary tumor resection in the discovery cohort. Preoperative samples were analyzed using small RNA sequencing to identify exosome-derived microRNAs associated with the presence of occult metastasis.

Treatment:

Diagnostic Test: EXOMIC small RNA sequencing

Discovery Cohort - ICC without Occult Metastasis

Description:

Patients with ICC who had no occult metastasis at the time of primary tumor resection in the discovery cohort. Preoperative samples from these patients were analyzed by small RNA sequencing and compared with those from patients with occult metastasis to identify candidate microRNAs.

Treatment:

Diagnostic Test: EXOMIC small RNA sequencing