Hepato-ProMet: Proteomic assay of metabolic progression from steatosis to hepatobiliary cancer development

Dr. David Hughes

Dr. David Hughes was awarded with a HRCI-HRB-Joint Funding Scheme research fellowship in Partnership with Breakthrough Cancer Research.

The incidence of liver cancer and cancers of the biliary tract (collectively termed hepatobiliary cancers; HBC) is rising worldwide, including in Ireland and Europe. These deadly cancers are often diagnosed late and have limited available treatments. Increasing incidence has been linked to unhealthy lifestyles. Here, we hypothesize that metabolic and liver dysfunction (i.e., metabolic syndrome, hepatic accumulation of toxic lipids, inflammation), as a direct result of obesity and unhealthy dietary/lifestyle patterns, together promote HBC.
To address our hypothesis, we will compare metabolic profiles among subjects with progressive liver disease, metabolic syndrome, and obesity and how these conditions interactively promote HBC development. We will further evaluate how unhealthy dietary and lifestyle habits impact these processes. We will use existing data from well-configured Irish and French clinical liver disease studies (fatty and inflamed liver diseases, liver cancers (n=330), and controls (n=330, including healthy individuals and bariatric surgery patients treated for obesity), and a HBC case-control study nested within a pan-European cohort (EPIC), where data and biospecimens from 515 HBC cases and matched controls (1:1) were collected from several years prior to diagnosis.
We will specifically measure the proteins that are attached to ‘good cholesterol’ (or HDL particles) using a newly developed blood test at UCD (MetHealth). HDL particles are made by and secreted from the liver; measuring the proteins on HDL therefore provides a mirror to the liver (particularly detecting metabolic and inflammatory dysfunction in the liver) but in an easily accessible blood test. We hypothesize that the proteins on HDL will change with liver disease/cancer progression and will serve as an early indicator of HBC, and risk thereof.
The findings will provide novel biomarkers to identify patients with metabolic and liver dysfunction and those at risk of developing HBC. This will enhance understanding of HBC development, diagnosis, and public cancer prevention policy.