Blood biomarkers in TGF-β pathway identify hidden liver cancer risk

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A new research paper is published Genes and Cancer On February 5, 2023, “Blood proteomic markers mechanistically based on the TGF-β pathway stratify the risk of hepatocellular carcinoma in patients with cirrhosis.”

Hepatocellular carcinoma (HCC) is the third leading cause of death from cancer worldwide but is often diagnosed at an advanced curable stage. Yet, despite the urgent need for blood-based biomarkers for early detection, few studies capture ongoing biology to identify risk-stratifying biomarkers.

In this new study, researchers Dr Jian Jiang, Krishanu Bhowmik, Kirti Shetty, Kazufumi Ohshiro, Xiaochun Yang, Linda L. Wong, Herbert Yu, Patricia S. Latham, Sanjaya K. Satapathi, Christina Brennan, Richard J. Dima, Nyasha Chambuye, Gulru Sharifova, Felanza, Sahara John, James M. Crawford, Hai Huang, Srinivasan Dasarathi, Adrian R. Kreiner, IU R. He, Richard L. Amdur, And Lopa is mixedThe 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 Lombardy Comprehensive Cancer Center fills this gap using the TGF-β pathway as its biological role in liver disease and cancer, established through rigorous animal models and human studies.

“Changes in the TGF-β signaling pathway may reflect the progression from cirrhosis to cancer to fibrosis in the liver. Thus, we hypothesize that TGF-β pathway-enriched biomarkers may serve as biomarkers in the development of HCC and stratify patients at risk.” for Additionally, we hypothesized that the integrated animal model-to-human study program would generate new TGF-β driven mechanistic biomarkers that may be valuable in providing additional biomarkers that may stratify the risk of HCC.”

Using machine learning methods with blood levels of 108 proteomic markers in the TGF-β family, the team found a pattern that distinguished HCC from non-HCC in a cohort of 216 cirrhosis patients, which they referred to as TGF-β based protein markers. 31 markers for early detection of HCC (TPEARLE). Notably, 20% of patients with cirrhosis alone presented an HCC-like pattern, suggesting that they may be a group that has not yet been detected or is at high risk for developing HCC.

In addition, the researchers found two other biologically relevant markers, myostatin and pyruvate kinase M2 (PKM2), which were significantly associated with HCC. They examined these for risk stratification of HCC in multivariable models adjusted for demographic and clinical variables as well as batch and site. These markers reflect the ongoing biology in the liver.

“They potentially indicate the presence of HCC early in its evolution and before it manifests as a detectable lesion, thereby providing a set of markers that may be able to stratify risk for HCC.”


Journal Reference:

Jiang, X., etc (2024). Blood proteomic markers mechanistically based on the TGF-β pathway stratify the risk of hepatocellular carcinoma in patients with cirrhosis. Genes and Cancer.

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