HCC Screening Using DNA Methylation Changes in ctDNA

HKGepitherapeutics403 enrolled

Overview

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.

Study Type

OBSERVATIONAL

Enrollment

403

Conditions

Hepatocellular Carcinoma

Interventions

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

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (1)

Infectious Diseases Division

Dhaka, Bangladesh

Outcomes

Primary Outcomes

Calculation of M Scores and HCC Probability Scores

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

Time frame: 6 months to 1 year

Data from ClinicalTrials.gov

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