Home Medizin Blutbiomarker im TGF-β-Signalweg identifizieren verstecktes Leberkrebsrisiko

Blutbiomarker im TGF-β-Signalweg identifizieren verstecktes Leberkrebsrisiko

von NFI Redaktion

On February 5, 2023, a new research paper titled „Mechanistically-based Blood Proteomic Markers in the TGF-β Signaling Pathway Stratify the Risk of Hepatocellular Carcinoma in Patients with Cirrhosis“ was published in Gene & Cancer.

Hepatocellular carcinoma (HCC) is the third most common cancer-related cause of death worldwide, but it is often diagnosed only in an advanced, incurable stage. Despite the urgent need for blood-based biomarkers for early detection, few studies capture the current biology to identify risk-stratifying biomarkers.

In this new study, researchers Xiyan Xiang, Krishanu Bhowmick, Kirti Shetty, Kazufumi Ohshiro, Xiaochun Yang, Linda L. Wong, Herbert Yu, Patricia S. Latham, Sanjaya K. Satapathy, Christina Brennan, Richard J. Dima, Nyasha Chambwe, Gulru Sharifova, Fellanza Cacaj, Sahara John, James M. Crawford, Hai Huang, Srinivasan Dasarathy, Adrian R. Krainer, Aiwu R. He, Richard L. Amdur, and Lopa Mishra from various medical research institutions closed this gap using the TGF-β signaling pathway due to its biological role in liver diseases and cancer, demonstrated through rigorous animal models and human studies.

„Changes in the TGF-β signaling pathway could reflect a continuum from fibrosis to cirrhosis to liver cancer. Therefore, we hypothesize that TGF-β-enriched biomarkers could serve as biomarkers in the development of HCC and stratify at-risk patients,“ the authors stated.

Using machine learning methods with blood levels of 108 proteomic markers of the TGF-β family in a cohort of 216 patients with cirrhosis, the team identified a pattern that distinguishes HCC from non-HCC, which they call TGF-β-based Protein markers for Early Recognition of Liver Cancer (TPEARLE), consisting of 31 markers. Notably, 20 of the patients with cirrhosis alone exhibited an HCC-like pattern, suggesting that they may be a group with either undetected HCC or a high risk for developing HCC.

Additionally, the researchers found two other biologically relevant markers, Myostatin and Pyruvate Kinase M2 (PKM2), that were significantly associated with HCC. They tested these for HCC risk stratification in multivariable models, adjusted for demographic and clinical variables, as well as batch and site. These markers reflect ongoing biology in the liver and may indicate the presence of HCC at the early stages of its development before it manifests as a recognizable lesion.

Source:

Journal reference:

Xiang, X., et al. (2024). Mechanistically-based Blood Proteomic Markers in the TGF-β Signaling Pathway Stratify the Risk of Hepatocellular Carcinoma in Patients with Cirrhosis. Gene & Cancer. doi.org/10.18632/genesandcancer.234.

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