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

Study on Recurrence Monitoring of Hepatocellular Carcinoma With 5-Hydroxymethylcytosine Based on hmC-Seal Technology

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.

Study Overview

• Status: Unknown
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Diagnostic test: 5hmC profile in plasma cell-free DNA after liver resection

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.

• Study Type: Observational
• Enrollment (Anticipated): 300

Contacts and Locations

• Study Contact: Name: Jia Fan, MD&PhD; Phone Number: +86 21 64041990; Email: fan.jia@zs-hospital.sh.cn

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Recruiting
      • ZhongShan Hospital
      • Contact: Jia Fan, MD&PhD; Phone Number: +86 21 64041990; Email: fan.jia@zs-hospital.sh.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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.

Description

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 Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Retrospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
serum AFP negative HCC patients; Patients who received liver resection within 3 months;; Hepatocellular carcinoma confirmed pathologically;; Serum alpha-fetoprotein level lower than 20ng/ml before hepatectomy.	Diagnostic test: 5hmC profile in plasma cell-free DNA after liver resection; Peripheral blood is drawn every 3 months after liver resection for 5hmC test (Time frame: 2 years or until tumor recurrence).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time of hepatocellular carcinoma recurrence	Time from the day of liver resection to the day of clinical diagnosis of recurrence	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
5hmC level in recurrence-related cfDNA after liver resection	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.	2 years or until tumor recurrence
Serum alpha-fetoprotein level after liver resection		2 years or until tumor recurrence
Adverse effect of 5hmC blood test	Any adverse effect of the test is to be recorded.	2 years

Collaborators and Investigators

• Sponsor: Shanghai Zhongshan Hospital
• Investigators: Study Director: Jia Fan, MD&PhD, Shanghai Zhongshan Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2018
• Primary Completion (Anticipated): December 31, 2019
• Study Completion (Anticipated): March 30, 2020

Study Registration Dates

• First Submitted: April 1, 2018
• First Submitted That Met QC Criteria: April 9, 2018
• First Posted (Actual): April 10, 2018

Study Record Updates

• Last Update Posted (Actual): April 10, 2018
• Last Update Submitted That Met QC Criteria: April 9, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: Liquid biopsy; Cell-free DNA; Recurrence Monitoring; 5-Hydroxymethylcytosine
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Disease Attributes; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Recurrence
• Other Study ID Numbers: 5hmc HCC monitoring

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No