2024-02-10 04:16:42
A new research paper was published in Genes and cancer On February 5, 2023, titled, “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 most common cause of death from cancer worldwide, but is often diagnosed at an advanced, incurable stage. However, despite the urgent need for blood-based biomarkers for early detection, few studies capture ongoing biology to identify biomarkers from risk strata.
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 Dasarathi, Adrian R. Kreiner, Ivo R.H., Richard L. Amador, and Lopa MishraFrom the Feinstein Institute for Medical Research, Cold Spring Harbor Laboratory, University of Maryland, University of Hawaii, University of Hawaii Cancer Center, George Washington University, North Shore University Hospital, Northwell Health, Hofstra Northwell School of Medicine, Cleveland Clinic, and Cancer Center Georgetown Lombardi’s comprehensive, address this gap using the TGF-β pathway because of its biological role in liver disease and cancer, which has been established through rigorous animal models and human studies.
“Changes in the TGF-β signaling pathway can reflect a continuum from fibrosis to cirrhosis to liver cancer. Therefore, we hypothesize that the biomarkers enriched in the TGF-β pathway may serve as biomarkers in the evolution of HCC and to stratify patients at risk for HCC. In addition, we hypothesized that the integrated program of models for studies between Animals to humans will yield new mechanistic biomarkers driven by TGF-β that could be valuable in deriving additional biomarkers that can 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 differentiating HCC from non-HCC in a group of 216 patients with cirrhosis, which they refer to as TGF-β-based protein markers. for the early detection of HCC (TPEARLE) which includes 31 markers. Of note, 20 of the patients with cirrhosis alone presented a HCC-like pattern, suggesting that they may be a group with undetected HCC or at high risk of 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 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.
“They may indicate the presence of HCC early in its development and before it manifests as an identifiable lesion, thus providing a set of markers that may be able to stratify the risk of HCC.”
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