HCC Screening Using DNA Methylation Changes in ctDNA

Hepatocellular Carcinoma (HCC) is the fifth most common cancer world-wide. It is particularly prevalent in Asia, and its occurrence is highest in areas where hepatitis B is prevalent, indicating a possible causal relationship. Follow up of high-risk populations such as chronic hepatitis patients and early diagnosis of transitions from chronic hepatitis to HCC would improve cure rates. In most cases HCC is detected late resulting in increased mortality and morbidity.

The purpose of this study is to develop and test non-invasive biomarkers based on methylation changes in PBMC and circulated tumor DNA in hepatocellular carcinomas patients.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Hepatocellular Carcinoma Adenocarcinoma Carcinoma Carcinoma, Hepatocellular Digestive System Diseases Digestive System Neoplasms Liver Diseases Liver Neoplasms Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Glandular and Epithelial

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Infectious Diseases Division

Dhaka, Bangladesh

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Confirmed diagnosis of HCC by EASL-EORTC guidelines
Confirmed hepatitis B diagnosis for HepB patients using AASLD practice guidelines.

Exclusion criteria

for HCC:

Cirrhosis, any other known inflammatory disease (bacterial or viral infection with the exception of hepatitis B or C, diabetes, asthma, autoimmune disease, active thyroid disease) which could alter T cells and monocytes characteristics
Other cancers.

Exclusion criteria

for HepB:

Diagnosis of HCC or any other cancer.

Exclusion criteria

for Healthy Controls:

Any known inflammatory or infectious disease including HepB and HepC
Chronic diseases,
Cancer
Medications or drug use

Treatment and study plan

ctDNA methylation in and it's Correlation wth Development and prediction of HCC

Diagnostic Test

Blood sample from patients with HCC, healthy individuals and individuals with hepatitis B will be collected, and DNA will extracted from PBMC and circulated tumor DNA will be subjected to bisulfite conversion. DNA from PBMC DNA will be analyzed with primers developed for the AHNAK-STAP1 genes. Plasma samples will be subjected to EZ direct DNA extraction and bisulfite conversion kit and will be amplified with primers developed to amplify the target regions. DNA will be used for the subsequent PCR amplification with specific primer to generate PCR amplicon for sequencing using a double PCR procedure. The product of PCR reaction will be subjected to indexed MiSeq Next-Generation sequencing that will allow us quantify DNA methylation level.

Primary outcomes

Calculation of M Scores and HCC Probability Scores

Time frame: 6 months to 1 year

We normalized median methylation values (range 0-100) for 'HCC-detect' (Hepatocellular Carcinoma Detection) and 'HCC-spec' (Hepatocellular Carcinoma Specificity). 'HCC-detect' is derived from CHFR, VASH2, CCNJ, and GRID2IP regions, aiming to broadly identify HCC. Theoretical range is -6.6438 to 8.6438, with observed -3.541 to 7.65; higher scores indicate increased HCC likelihood. 'HCC-spec', focusing on the F12 region, differentiates HCC from 31 other cancers and normal cells, with theoretical range -3.3219 to 6.64385 (observed -3.3219 to 6.6297). Higher scores signify greater HCC specificity. Both scores, modeled via logistic regression in Prism, predict HCC probability, linking higher scores with higher HCC likelihood or specificity

Sponsors and collaborators

Lead sponsor

HKGepitherapeutics

Industry

Collaborators

International Centre for Diarrhoeal Disease Research, Bangladesh

Registry information

Official study title

Clinical Trials on Detection of Hepatocellular Carcinoma With Non-invasive Method Based on DNA Methylation of Circulated Tumor DNA, PBMC and T Cells

Important dates

Study start: 2018
Primary completion: 2020
Study completion: 2020
First posted: Mar 30, 2018
Registry last updated: Jul 5, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

Completed