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Study on Recurrence Monitoring of Hepatocellular Carcinoma With 5-Hydroxymethylcytosine Test

Conditions
Hepatocellular Carcinoma
Interventions
Diagnostic Test: 5hmC profile in plasma cell-free DNA after liver resection
Registration Number
NCT03493763
Lead Sponsor
Shanghai Zhongshan Hospital
Brief Summary

In this study, investigators aim to find out how plasma 5hmC level changes in hepatocellular carcinoma patients after liver resection, and determine whether 5hmC can be used as a biomarker for HCC recurrence monitoring.

Detailed Description

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the third leading cause of cancer-related death worldwide. Liver resection is a common treatment for HCC. However, even after successful surgical resection, most patients suffered from recurrence or progression of the tumor. Because clinical staging systems cannot precisely predict the outcome of patients with HCC, it's of great interest to search biomarkers for HCC. Among them, alpha-fetoprotein (AFP) is the most well-studied. However, the applicability of AFP for HCC after surgical resection of tumor is still uncertain.

The discovery of cell-free DNA (cfDNA) originating from different tissues in the circulating blood has revolutionary potential for the clinic. Liquid biopsy-based biomarkers and detection tools offer substantial advantages over existing diagnostic and prognostic methods, including being minimally invasive. They thus have a cost-efficient potential to promote higher patient compliance and clinical convenience to enable dynamic monitoring.

5-hydroxymethylcytosine (5hmC) is the intermediate of active demethylation from 5-methylcytosine. 5hmC not only marks active demethylation but also serves as a relatively stable DNA mark that plays distinct epigenetic roles. Recent genome-wide sequencing maps of 5hmC in various mammalian cells and tissues support its role as a marker for gene expression. Previous studies have established 5hmC-Seal technology for 5hmC profiling in cfDNA and showed that the differentially enriched 5hmC regions in cfDNA are excellent markers for solid tumors.

In this study, investigators aim to find out how plasma 5hmC profile changes in hepatocellular carcinoma patients after liver resection, and determine whether 5hmC can be used as a biomarker for HCC recurrence monitoring.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
300
Inclusion Criteria
  1. Patients who received liver resection within 3 months;
  2. Hepatocellular carcinoma confirmed pathologically;
  3. Serum alpha-fetoprotein level lower than 20ng/ml before hepatectomy.
Exclusion Criteria
  1. Patients with macroscopic tumor remnants;
  2. Patients with other diseases which may affect the observation mentioned here;
  3. Patients with medical history of other malignant tumors;
  4. Pregnant or nursing women.

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
serum AFP negative HCC patients5hmC profile in plasma cell-free DNA after liver resection1. Patients who received liver resection within 3 months; 2. Hepatocellular carcinoma confirmed pathologically; 3. Serum alpha-fetoprotein level lower than 20ng/ml before hepatectomy.
Primary Outcome Measures
NameTimeMethod
Time of hepatocellular carcinoma recurrence2 years

Time from the day of liver resection to the day of clinical diagnosis of recurrence

Secondary Outcome Measures
NameTimeMethod
Serum alpha-fetoprotein level after liver resection2 years or until tumor recurrence
Adverse effect of 5hmC blood test2 years

Any adverse effect of the test is to be recorded.

5hmC level in recurrence-related cfDNA after liver resection2 years or until tumor recurrence

Peripheral blood is drawn every 3 months after liver resection. 5hmc level in cfDNA in particular recurrence-related genes is tested by cfDNA sequencing and calculated by feature counts.

Trial Locations

Locations (1)

Zhongshan Hospital

🇨🇳

Shanghai, Shanghai, China

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