HCC Screening Using DNA Methylation Changes in ctDNA

Completed

Interventions: Diagnostic Test: ctDNA methylation in and it's Correlation wth Development and prediction of HCC

Brief Summary: 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.

Recruitment & Eligibility

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:

Exclusion Criteria for Healthy Controls:

Exclusion Criteria

Not provided

Arm && Interventions

Group	Intervention	Description
HCC Cases	ctDNA methylation in and it's Correlation wth Development and prediction of HCC	This group will include 350 in stage 0, stage A, stage B, Stage C+D of hepatocellular carcinoma. HCC staging will be diagnosed according to EASL-EORTC Clinical Practice Guidelines: Management of hepatocellular carcinoma
Healthy	ctDNA methylation in and it's Correlation wth Development and prediction of HCC	This group will include 50 healthy sex and age matched controls.
chronic hepatitis B	ctDNA methylation in and it's Correlation wth Development and prediction of HCC	This group will include 50 with hepatitis B subjects and the diagnoses will be based on AASLD practice guideline.

Primary Outcome Measures

Name	Time	Method
Calculation of M Scores and HCC Probability Scores	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

Secondary Outcome Measures