Overview
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.
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.
Eligibility
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.