Project for Multi-Omics-Based Early Detection of Hepatocellular Carcinoma (PROMETHEA Study)

Liver cancer is a major global health challenge, ranking as the 5th leading cause of cancer-related deaths in the U.S. and 3rd worldwide, with hepatocellular carcinoma (HCC) accounting for ~75% of cases. Incidence has more than tripled since 1980, and death rates have risen by ~2% annually, highlighting the need for improved detection and treatment. Prognosis remains poor: over 50% of HCC cases are diagnosed at stage IV, with a 1-year survival below 30%, whereas early-stage HCC (stages I-II) can achieve up to 74% 5-year survival with curative interventions. Major risk factors include viral hepatitis (HBV, HCV), alcohol abuse, obesity, type 2 diabetes, and non-alcoholic fatty liver disease (NAFLD), with non-viral HCC increasing in prevalence, particularly in Western countries. Screening programs target high-risk populations but miss many asymptomatic or average-risk individuals, contributing to late-stage diagnoses.

Biomarker discovery holds promise for improving early detection. Alpha-fetoprotein (AFP), the most widely used biomarker, has limited sensitivity for early-stage HCC (39-64%).

This study seeks to validate a panel of more accurate and non-invasive biomarkers in preoperative blood samples. Accurate early detection of HCC would help provide clear criteria for treatment decisions, such as timely surgical intervention or the addition of adjuvant chemotherapy.

Inclusion criteria

• Adults aged 18 to 100 years.
• A histologically confirmed diagnosis of hepatocellular carcinoma.
• A clinically diagnosed as chronic liver disease, including chronic hepatitis or liver cirrhosis, without evidence of hepatocellular carcinoma.
• Healthy volunteers without known liver disease or malignancy.
• Received standard diagnostic and staging procedures as per local guidelines
• Availability of blood or other biospecimens.
• Ability to provide written informed consent.

Exclusion criteria

• Lack of or inability to provide informed consent
• History of other active malignancies within the past 5 years
• Previous liver transplantation
• Severe systemic infection or inflammatory disease at the time of enrollment
• Inadequate sample quality or quantity