New insights into biomarkers and risk stratification to predict hepatocellular cancer

Katrina Li, The Institute for Bioelectronic Medicine, Feinstein Institutes for Medical Research & Cold Spring Harbor Laboratory, Department of Medicine, Division of Gastroenterology and Hepatology, Northwell Health, NY, 11030, USA.
Brandon Mathew, The Institute for Bioelectronic Medicine, Feinstein Institutes for Medical Research & Cold Spring Harbor Laboratory, Department of Medicine, Division of Gastroenterology and Hepatology, Northwell Health, NY, 11030, USA.
Ethan Saldanha, The Institute for Bioelectronic Medicine, Feinstein Institutes for Medical Research & Cold Spring Harbor Laboratory, Department of Medicine, Division of Gastroenterology and Hepatology, Northwell Health, NY, 11030, USA.
Puja Ghosh, The Institute for Bioelectronic Medicine, Feinstein Institutes for Medical Research & Cold Spring Harbor Laboratory, Department of Medicine, Division of Gastroenterology and Hepatology, Northwell Health, NY, 11030, USA.
Adrian R. Krainer, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, 11724, USA.
Srinivasan Dasarathy, Division of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH, 44106, USA.
Hai Huang, Center for Immunology and Inflammation, Feinstein Institutes for Medical Research, Donald and Barbara Zucker School of Medicine at Hofstra, Northwell Health, Manhasset, NY, 11030, USA.
Xiyan Xiang, The Institute for Bioelectronic Medicine, Feinstein Institutes for Medical Research & Cold Spring Harbor Laboratory, Department of Medicine, Division of Gastroenterology and Hepatology, Northwell Health, NY, 11030, USA. xxiang@northwell.edu.
Lopa Mishra, The Institute for Bioelectronic Medicine, Feinstein Institutes for Medical Research & Cold Spring Harbor Laboratory, Department of Medicine, Division of Gastroenterology and Hepatology, Northwell Health, NY, 11030, USA. LMishra1@northwell.edu.

Document Type

Journal Article

Publication Date

4-23-2025

Journal

Molecular medicine (Cambridge, Mass.)

Volume

31

Issue

1

DOI

10.1186/s10020-025-01194-6

Keywords

Biomarker; Cirrhosis; Early diagnosis; Liver cancer; Risk stratify

Abstract

Hepatocellular carcinoma (HCC) is the third major cause of cancer death worldwide, with more than a doubling of incidence over the past two decades in the United States. Yet, the survival rate remains less than 20%, often due to late diagnosis at advanced stages. Current HCC screening approaches are serum alpha-fetoprotein (AFP) testing and ultrasound (US) of cirrhotic patients. However, these remain suboptimal, particularly in the setting of underlying obesity and metabolic dysfunction-associated steatotic liver disease/steatohepatitis (MASLD/MASH), which are also rising in incidence. Therefore, there is an urgent need for novel biomarkers that can stratify risk and predict early diagnosis of HCC, which is curable. Advances in liver cancer biology, multi-omics technologies, artificial intelligence, and precision algorithms have facilitated the development of promising candidates, with several emerging from completed phase 2 and 3 clinical trials. This review highlights the performance of these novel biomarkers and algorithms from a mechanistic perspective and provides new insight into how pathological processes can be detected through blood-based biomarkers. Through human studies compiled with animal models and mechanistic insight in pathways such as the TGF-β pathway, the biological progression from chronic liver disease to cirrhosis and HCC can be delineated. This integrated approach with new biomarkers merit further validation to refine HCC screening and improve early detection and risk stratification.

Department

Surgery

Link to Full Text

Share

COinS