Exosome-derived Extrahepatic Metastasis Detection By Liquid Biopsy In Colorectal Cancer Liver Metastases
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 500
- 试验地点
- 1
- 主要终点
- Sensitivity
研究概览
简要总结
Colorectal cancer is the third most common malignancy worldwide, and prognosis largely depends on how effectively metastatic disease is managed. The liver is the most frequent and prognostically important site of metastasis, and patients responding well to chemotherapy may become candidates for curative hepatic resection. However, the presence of extrahepatic metastasis (EHM) critically influences treatment eligibility and survival. Although clinical scores such as the Fong and Beppu systems include EHM as a determinant, its detection by imaging remains limited, especially for small or occult lesions. Accurate identification of EHM is also essential when considering liver transplantation for unresectable colorectal liver metastases (CRLM), where EHM remains an exclusion criterion.
The EXELION Study aims to develop a non-invasive diagnostic model using serum exosomal microRNAs (miRNAs) to detect both hepatic and extrahepatic metastases in patients with CRLM. By integrating circulating miRNA profiling with machine learning-based analysis, this study seeks to supplement imaging diagnostics, improve treatment stratification, and enhance clinical decision-making for metastatic colorectal cancer.
详细描述
Despite improvements in diagnostic imaging-such as CT, MRI, and PET-CT-the sensitivity of EHM detection remains limited, particularly for small or occult lesions in the lung, peritoneum, or lymph nodes. As a result, patients may be inappropriately excluded from curative surgery or exposed to non-beneficial interventions. Thus, there is a pressing need for novel, non-invasive biomarkers capable of detecting EHM with higher accuracy than imaging alone.
MicroRNAs (miRNAs), especially those encapsulated within exosomes, have emerged as stable and reproducible biomarkers reflecting tumor dynamics. Recent studies have shown that circulating miRNA signatures are associated with liver metastasis, therapeutic response, and recurrence risk in CRC. However, their utility for detecting extrahepatic metastasis has not yet been validated in clinical cohorts.
In this research effort, the investigators will leverage small RNA sequencing and machine learning to develop a predictive model for the presence of hepatic and extrahepatic metastases in patients with CRLM. The research plan will consist of three phases:
- A discovery phase, identifying candidate miRNAs associated with the presence of EHM using next-generation sequencing (NGS) or microarray-based profiling of serum exosomal miRNAs.
- A model development phase, establishing a quantitative reverse transcription PCR (RT-qPCR) assay and training a predictive algorithm.
- A validation phase, independently testing the predictive accuracy of the model in an external cohort.
This diagnostic framework is provisionally termed "EXELION" (Exosome-derived Extrahepatic Metastasis Detection by LIquid Biopsy in Colorectal Cancer Liver Metastases). At the end of this study, the EXELION assay is expected to serve as a non-invasive tool to assist clinical decision-making by accurately predicting the presence of extrahepatic metastasis in patients with CRLM.
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
- •Adults (≥18 years old)
- •Histologically- or cytologically-confirmed colorectal cancer that is metastatic
- •Availability of pre-treatment plasma samples
- •Written informed consent provided
- •Sufficient clinical and imaging data to determine presence/absence of extrahepatic metastasis
排除标准
- •Prior malignancies within 5 years
- •Poor sample quality or hemolysis
- •Inability to provide informed consent
研究组 & 干预措施
Extrahepatic liver metastasis patients(Discovery Cohort)
Patients with colorectal liver metastases (CRLM) who have confirmed extrahepatic metastasis at the time of diagnosis or treatment planning, included in the first (discovery) cohort.
Extrahepatic liver metastasis patients(Training Cohort)
Extrahepatic liver metastasis patients (Training Cohort) Group/Cohort Description: Patients with colorectal liver metastases (CRLM) who have confirmed extrahepatic metastasis at the time of diagnosis or treatment planning, included in the first (training) cohort.
干预措施: EXELION (Other)
Non-extrahepatic liver metastasis patients(Discovery Cohort)
Group/Cohort Description: Patients with colorectal liver metastases (CRLM) who do not have confirmed extrahepatic metastasis at the time of diagnosis or treatment planning, included in the first (discovery) cohort.
干预措施: EXELION (Other)
Non-extrahepatic liver metastasis patients (Training Cohort)
Group/Cohort Description: Patients with colorectal liver metastases (CRLM) who do not have confirmed extrahepatic metastasis at the time of diagnosis or treatment planning, included in the (training) cohort.
干预措施: EXELION (Other)
Extrahepatic liver metastasis patients (Validation Cohort)
Group/Cohort Description: Patients with colorectal liver metastases (CRLM) who have confirmed extrahepatic metastasis at the time of diagnosis or treatment planning, included in the second, independent, validation cohort
Non-extrahepatic liver metastasis patients (Validation Cohort)
Group/Cohort Description: Patients with colorectal liver metastases (CRLM) who do not have confirmed extrahepatic metastasis at the time of diagnosis or treatment planning, included in the second, independent, validation cohort
干预措施: EXELION (Other)
结局指标
主要结局
Sensitivity
时间窗: Through study completion, an average of 1 year
True positive rate: the probability of a positive test result, conditioned on the individual truly being positive
次要结局
- Specificity(Through study completion, an average of 1 year)
- Accuracy(Through study completion, an average of 1 year)