Machine Learning-based Exosome Liquid Biopsy Enables Stratification of Occult Metastasis Risk in Patients With Intrahepatic Cholangiocarcinoma
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 230
- 试验地点
- 1
- 主要终点
- Recurrence Free Survival
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Retrospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •Extrahepatic cholangiocarcinoma or gallbladder cancer.
- •Synchronous non-ICC malignancy.
- •Inadequate clinical follow-up.
- •Inability to consent.
研究组 & 干预措施
Training Cohort - ICC with Occult Metastasis
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.
干预措施: EXOMIC assay (qRT-PCR validation) (Diagnostic Test)
Training Cohort - ICC without Occult Metastasis
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.
干预措施: EXOMIC assay (qRT-PCR validation) (Diagnostic Test)
Validation Cohort - ICC with Occult Metastasis
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.
干预措施: EXOMIC assay (qRT-PCR validation) (Diagnostic Test)
Validation Cohort - ICC without Occult Metastasis
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.
干预措施: EXOMIC assay (qRT-PCR validation) (Diagnostic Test)
Discovery Cohort - ICC with Occult Metastasis
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.
干预措施: EXOMIC small RNA sequencing (Diagnostic Test)
Discovery Cohort - ICC without Occult Metastasis
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.
干预措施: EXOMIC small RNA sequencing (Diagnostic Test)
结局指标
主要结局
Recurrence Free Survival
时间窗: 3 years
The time period from surgery to recurrence of ICC.
次要结局
- Overall Survival(5 years)