Intrahepatic Cholangiocarcinoma (Icc)
Conditions
Keywords
Exosomal miRNA, ICC, Liquid Biopsy, Occult metastasis, Tumor recurrence, Liver cancer
Brief 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.
Interventions
DIAGNOSTIC_TESTEXOMIC 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_TESTEXOMIC 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.
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
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recurrence Free Survival | 3 years | The time period from surgery to recurrence of ICC. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | 5 years | Time from surgery to death from any cause |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORAjay Goel, PhD
City of Hope Medical Center
Outcome results
None listed