Hepatic and Circulating microRNAs miR-221 and miR-222 Expression and Its Clinical Significance in Hepatocellular Carcinoma (HCC)
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 入组人数
- 10
- 试验地点
- 2
- 主要终点
- presence of miR-221 and mR-222 in the blood
研究概览
简要总结
Hepatocellular carcinoma (HCC) is the most frequent primary tumour of the liver and is the third cause of cancer-related mortality worldwide. Depending on the stage of the disease, the treatment options are surgery, liver transplantation, chemotherapy or radiotherapy.
Recently, scientific research has focused on small molecules called microRNAs which are produced by human cells and can be released in the blood. They have a role in cell proliferation and are found to be dysregulated in different types of cancer.
It has been shown that microRNAs have a role in the development of HCC but it is unknown if these molecules can be used as markers for diagnosis and survival in HCC.
In particular, microRNAs miR-221 and miR-222 are dysregulated in the tumoral tissues in about 80% of patients with HCC. This can be assessed on tissues from liver biopsies or surgical specimens, both invasive approaches. Only few studies showed the presence of microRNAs in the blood of patients with HCC but it is unknown if there is a correlation between tumoral tissue expression and circulating levels.
The aim of this study is to evaluate if these two microRNAs are expressed not only in the tumoral tissues but also in the blood from cancer patients, and in different amounts compared to circulating levels in healthy individuals. A correlation between tumoral tissue and blood levels will also be evaluated.
Should this evaluation show a strong correlation and reliability of circulating microRNAs in the diagnosis and follow up of HCC, future clinical trials targeting these microRNAs and their related pathways might benefit from this being adopted as conventional practice instead of the need of assessing tissue levels from liver biopsies.
The results of this pilot study will bring preliminary results as a first step for future analysis on a larger cohort of patients.
详细描述
- Background & Rationale Hepatocellular carcinoma (HCC) is the sixth most prevalent cancer worldwide, and is the third cause of cancer-related mortality.
Surgical resection remains the best curative treatment option for patients with clinical Barcelona-Clinic Liver Cancer (BCLC) stage A disease and it has shown benefits even in the more advanced stage B with multifocal disease or limited vascular invasion.
Despite curative treatments offering a 5-year survival rate of 50-70%, recurrence rates at 5 years after surgery are as high as 70%. Therefore, more efforts are needed in order to identify prognostic factors for recurrence and survival.
MicroRNAs are a class of small non-coding RNAs molecules, which act as key regulators of cell proliferation, differentiation, apoptosis and embryonic development, finely tuning gene expression at post-transcriptional level. They act as oncogenes or tumor suppressors depending on the target genes. In HCC, it has been reported the upregulation or downregulation of a few cluster of microRNAs, with a subsequent activation of molecular networks such as b-catenin, Ras, TGF-b, JAK/STAT and creation of a highly controlled feedback mechanism.
Their involvement in carcinogenesis represents an important area of investigation for the development of their clinical applications: diagnostics, monitoring and therapeutics. MicroRNA profiles can distinguish between normal and cancerous tissue, identify tissue of origin and also discriminate different subtypes or specific oncogenic abnormalities. Indeed, microRNA mis-expression patterns are more accurate in identifying the origin of tumours that are otherwise difficult to be determined, suggesting that tumours more clearly maintain a unique tissue microRNA expression profile.
研究设计
- 研究类型
- Observational
- 观察模型
- Other
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •hepatocellular carcinoma, not eligible for liver transplant undergoing surgical resection
排除标准
- •extrahepatic disease, other primary tumour
结局指标
主要结局
presence of miR-221 and mR-222 in the blood
时间窗: 6 months
To evaluate the presence of miR-221 and mR-222 in the blood of patients with HCC compared to age-matched healthy controls
次要结局
- correlation of expression of miR-221 and miR-222 in tissue and blood samples(6 months)