Mechanistically-based blood proteomic markers may be able to stratify risk for hepatocellular carcinoma
Hepatocellular carcinoma (HCC) is the third leading cause of death from cancer worldwide but is often diagnosed at an advanced incurable stage. Yet, despite the urgent need for blood-based biomarkers for early detection, few studies capture ongoing biology to identify risk-stratifying biomarkers.
In a new study published in Genes & Cancer, researchers have made significant progress in addressing this gap by focusing on the TGF-β pathway, known for its biological role in liver disease and cancer. Using rigorous animal models and human studies, the researchers explored this pathway to identify mechanistically-based blood proteomic markers that may be able to stratify the risk for hepatocellular carcinoma in patients with cirrhosis.
Alterations in the TGF-β signaling pathway could reflect a continuum of fibrosis to cirrhosis to cancer in the liver. Thus, we hypothesize that the TGF-β pathway-enriched biomarkers may serve as biomarkers in the evolution of HCC and stratify patients at risk for HCC. In addition, we hypothesized that the integrated animal model-to-human studies program would yield new TGF-β driven mechanistic biomarkers that could be valuable in yielding additional biomarkers that could stratify the risk of HCC, explained the researchers.
Using machine learning methods, the research team analyzed the blood levels of 108 proteomic markers in the TGF-β family. In their study involving 216 patients with cirrhosis, they discovered a pattern that differentiates HCC from non-HCC, which they call TGF-β based protein markers for early detection of HCC (TPEARLE). These markers consist of 31 proteins and show promising potential for early detection.
Interestingly, among the patients with cirrhosis alone, 20 exhibited an HCC-like pattern, indicating that they may have undetected HCC or a high risk of developing the disease.
The researchers also identified two other biologically relevant markers, myostatin and pyruvate kinase M2 (PKM2), which were significantly associated with HCC. They further tested these markers for risk stratification of HCC in multivariable models adjusted for demographic and clinical variables. These markers provide insights into the ongoing biology of liver disease and may indicate the presence of HCC early in its progression.
These markers potentially indicate the presence of HCC early in its evolution and before it is manifest as a detectable lesion, thereby providing a set of markers that may be able to stratify risk for HCC, said the authors.
The study was conducted by a team of researchers from various institutions including The Feinstein Institutes for Medical Research, Cold Spring Harbor Laboratory, University of Maryland, University of Hawaii, University of Hawaii Cancer Center, The George Washington University, North Shore University Hospital, Northwell Health, Hofstra Northwell School of Medicine, Cleveland Clinic, and Georgetown Lombardi Comprehensive Cancer Center.
This groundbreaking research brings us closer to finding blood-based biomarkers that can detect HCC at an early stage, enabling clinicians to intervene sooner and potentially save lives. The TGF-β based protein markers identified in this study offer hope for improved risk stratification and early detection strategies for patients with cirrhosis and those at high risk of developing HCC.
As more studies are conducted and further advancements are made in the field of blood-based biomarkers, the dream of detecting and treating HCC in its most manageable stage could become a reality, paving the way for improved outcomes for patients worldwide.
