Development of a test for the early detection of liver cancer
In 2020 hepatocellular carcinoma (HCC) was the third most common cause of cancer-related deaths globally, with approximately 800.000 annual fatalities. HCC survival is low because of limited treatment options due to late diagnoses. Currently, HCC screening relies on ultrasonography, sometimes combined with serological alpha-fetoprotein measurement. Unfortunately, these screening strategies show a sensitivity of only 47% and 63%, respectively, for detection of early-stage HCC. Early-stage diagnosis greatly improves the likelihood that patients can benefit from tumour resection/ablation or liver transplantation. Therefore, to reduce HCC morbidity and mortality, there is a need for a better screening test for efficient and cost-effective HCC surveillance.
In a previous study, Levels Diagnostics identified 57 protein biomarkers together with the LUMC which, when integrated into predictive models in combinations of 6, could detect HCC with an AUC of >95% within a cohort of cirrhotic metabolic dysregulation-associated steatotic liver disease (MASLD) patients (38 with mostly early-stage HCC, 40 controls). These proteins were found using SomaScan proteomic assays to measure >7000 plasma concentrations.
In this project, we want to explore and validate the use of the identified protein markers for other important HCC etiologies, specifically viral hepatitis and alcoholic liver disease (ALD). Firstly, we want to conduct a discovery study in viral hepatitis-associated HCC patients, using SomaScan assays, and compare the results with our previous findings. Secondly, we will validate the previously found markers in an ALD cohort using enzyme- linked immunosorbent assays (ELISAs). We hypothesise that the previously identified markers could also be used for early-stage HCC detection in ALD-related HCC patients, as we suspect that ALD and MASLD are very closely related diseases.
If this project succeeds, the best-performing signature will be used for the development of an accurate, non-invasive test for early-stage HCC screening in cirrhosis patients.
