A New Biomarker for Detection of Minimal Residual Tumor in Hepatitis-B Virus Related Hepatocellular Carcinoma After Curative Therapies: The Cell-free Circulating HBV-host Chimera DNA Fragment
试验速览
- 阶段
- 不适用
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- vh-chimera DNA
研究概览
简要总结
Early stage HCC is treated by curative surgical resection or by local ablation (such as radio-frequency) as the current standard of care. The complete removal of clinical visible HCC is then confirmed by imaging by MRI or CT, or by a decline of tumor marker (AFP or PIVKA). However, despite an apparent complete removal of the HCC, those post-curative patients frequently develop tumor recurrence at a rate ranging 10-50% within the first year. The high rate of early HCC recurrence indicated a minimal residual HCC after the curative therapies in a significant proportion of patients. A better and more specific biomarker for detecting the residual HCC will improve the patients' prognosis prediction and therapeutic plan.
To detect the minimal residual HCC, a biomarker unique to the tumor is needed. Currently, the cell-free circulating DNA carrying tumor-specific somatic mutations has been advocated as a promising one. It has been applied to investigate the tumor responses or resistances to cancer therapy. However, currently it is restricted to detect or follow only large advanced cancer, because of the difficulty in separating or enriching the cfDNA with tumor-specific mutations from the cfDNA from normal cells. In this project, the investigators proposed that one class of somatic mutation in HBV-related HCC, namely the insertion mutagenesis by integrated HBV DNA, could be adopted to circumvent this difficulty. HBV DNA integration has been found in the chromosomes of about 90% of HBV-related HCC and the integration site is unique to individual HCC. The HBV-host junction DNA fragment from one HCC is therefore a tumor-specific biomarker. Such fragments can be released into the circulation as cell-free circulating DNAs, and the detection of the HBV-host chimera DNAs in the circulation is a reliable evidence for the presence of the tumor in the patient. Therefore the cf circulating HBV-host chimera DNA is proposed to assay any minimal residual HCC after curative therapies.
详细描述
Development stages:
Stage I: Identification of integrated HBV DNA sites in HBV-related HCC tissues. the investigators will develop either HBV-specific inverse PCRs or capture-sequencing protocols to identify HBV integrations sites in the tumor chromosomes. The viral-host junction sequences of individual HCC identified and used as the template for developing assays for detecting the same HBV-host chimera DNA fragment in the circulation.
Stage II: New platforms to accurately detect or even quantitate the circulating vh-chimera DNA fragment.
These tumor-specific vh-chimera DNA will only represent a tiny fraction of total cfDNAs. However, as these sequences of the tumor-specific vh-chimera DNA have been known from stage 1, the investigators may develop better and more specific assays for quantitation.
Stage III: Assays for cell-free tumor specific vh-chimera DNA applied to the blood samples from post-curative HCC patients.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Only
- 时间视角
- Prospective
入排标准
- 年龄范围
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •HBV-related HCC patients that receive surgical removal of tumor.
排除标准
- •unsuitable for surgery.
结局指标
主要结局
vh-chimera DNA
时间窗: week 4 after surgery.
Detection of the HBV-host chimera DNA in blood sample.----- one blood sampling at the time of HCC recurrence.
次要结局
- recurrence-free survival time ----measurement in weeks(from the date of surgery until the date of first documented HCC recurrence or date of death from any cause, whichever came first, assessed up to 24 months)
- Tumor size (measured in the longest dimension in cm)(after medical imaging or pathology report completion, up to 2 weeks.)
- tumor grade (Grades I-IV)(after medical imaging or pathology report completion, up to 2 weeks.)