Development of A Generic Blood Test Based on Gene Signatures To Diagnose Hepatocellular Carcinoma Patients

Completed

Conditions: Liver cell carcinoma,

Registration Number: CTRI/2023/10/058191

Lead Sponsor: Mohamed Rela

Brief Summary: Development of blood-based screening test that quantifies methylation levels and determines methylation patterns of cell free DNA (cfDNA) to assess the likelihood of a patient harbouring hepatocellular carcinoma (HCC). The panel is intended to be applicable for Screening for HCC

Liquid biopsies are now becoming a frequently used tool for various cancers. Fragments of DNA called as Cell free DNA (cfDNA) are shed into blood regularly. In the case of cancer, such fragments contain circulating tumor DNA (ctDNA) that are shed via tumor cell necrosis, apoptosis and active release of DNA that can be analysed to determine specific DNA aberrations. Recent advances in blood based liquid biopsies is revolutionizing the process of early detection of cancer, cancer recurrence and screening. Liquid biopsies offer several advantages over tissue biopsies such as but not limited to (i) collection of peripheral blood instead of surgical tissue removal and (ii) Ease of access to monitor the genetic and epigenetic aberrational status during therapy or post-surgery. In addition, monitoring of cfDNA may enable detection of tumor during early stages or recurrence wherein the imaging results are indeterminate.

In the case of HCC, early detection and recurrence monitoring has been limited. Traditional liver function tests and imaging techniques, while useful, often fail to detect early-stage disease or differentiate between disease severities. Currently, Alpha Fetal Protein (AFP) is the only blood-based diagnosis method used as a diagnostic tool for detection and surveillance of HCC and it is known that the clinical utility of the diagnostic tool is limited because of the low sensitivity. Therefore, use of molecular diagnostics to determine genetic and epigenetic aberrations is clinically significant for treatment and surveillance of HCC patients.

The study aims to develop and validate a screening tool that leverages epigenetic biomarkers for early liver disease detection, enabling timely diagnosis and personalized treatment strategies. Epigenetic alterations, such as DNA methylation and histone modifications, have emerged as promising biomarkers due to their sensitivity and specificity in detecting liver pathology. By integrating these biomarkers into a non-invasive screening approach, the test seeks to enhance early diagnosis, reduce healthcare costs, and improve prognostic accuracy.

HCC, the most common form of primary liver cancer, is associated with DNA hypermethylation. The test analyzes hypermethylation in to assess HCC risk. The test involves collecting blood, extracting cell-free DNA (cfDNA), and analysing methylation patterns.

This study will assess the effectiveness of epigenetic screening compared to conventional diagnostic methods, evaluating its clinical applicability in diverse populations. The findings could revolutionise liver disease management by providing a novel, accessible, and precise tool for early intervention, ultimately reducing the burden of liver-related morbidity and mortality worldwide.

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: All

Target Recruitment: 400

Inclusion Criteria

All patients with a diagnosis of hepatocellular carcinoma on imaging 2.
All patients with a suspicion of hepatocellular caricnoma based on imaging or tumour markers (elevated AFP, PIVKA) 3.
Patients undergoing surgery (resection or transplant) for hepatocellular carcinoma 4.
Patients undergoing palliative care modalities (chemotherapy, immunotherapy, embolisation etc) for hepatocellular carcinoma.

Exclusion Criteria

Age below 18 years, or above 80 years 2.
patients with liver tumors other than hepatocellular carcinoma 3.
Patients who refuse to enroll for the study.

Study & Design

Study Type: Observational

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To determine the mutational status of HCC patients to prognosticate the tumour	15 days, 1,3,6 months, 1 year, 18 months, 2 years

Secondary Outcome Measures

Name	Time	Method
To correlate and predict risk of recurrence with existing biomarkers - alpha fetoprotein and PIVKA	15 days, 1,3,6 months, 1 year, 18 months, 2 years

Trial Locations

Locations (1): Dr Rela Institute and Medical Centre
🇮🇳
Chennai, TAMIL NADU, India
Dr Rela Institute and Medical Centre
🇮🇳Chennai, TAMIL NADU, India
Dr Vasanthakumar Gunasekaran
Principal investigator
8861401250
vasanth_smc@yahoo.co.in