Clinical trial NCT03493763: Study on Recurrence Monitoring of Hepatocellular Carcinoma With 5-Hydroxymethylcytosine Test
Official title: Study on Recurrence Monitoring of Hepatocellular Carcinoma With 5-Hydroxymethylcytosine Based on hmC-Seal Technology
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Hepatocellular Carcinoma
Keywords: Recurrence Monitoring
5-Hydroxymethylcytosine
Liquid biopsy
Cell-free DNA
Lead sponsor: Shanghai Zhongshan Hospital
Sponsor class: OTHER
First posted: 2018-04-10
Enrollment: 300
Sex: ALL
Minimum age (years): 20
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: RETROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The population will be selected from patients who have received liver resection in the Liver Surgery Department of 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Time of hepatocellular carcinoma recurrence
timeFrame: 2 years
Secondary outcomes:
measure: 5hmC level in recurrence-related cfDNA after liver resection
timeFrame: 2 years or until tumor recurrence
measure: Serum alpha-fetoprotein level after liver resection
timeFrame: 2 years or until tumor recurrence
measure: Adverse effect of 5hmC blood test
timeFrame: 2 years
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Zhongshan Hospital
state: Shanghai
Study officials:
affiliation: Shanghai Zhongshan Hospital
name: Jia Fan, MD&PhD
role: STUDY_DIRECTOR
References: