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DeLIVER Work packages

Development of HCC early detection patient cohorts (Work package 1) consists of three ethically approved research projects that recruit cirrhosis and/or HCC patient groups in order to address different aspects of early HCC development by characterising the cirrhotic liver in patients with and without HCC through liver biopsy, surgery and fine needle aspiration (DELPHI study, N=60 participants), by identifying biomarkers in urine, blood and liver tissue as well as from liver Imaging which are associated with early development of HCC (SELiNa study, N=250 participants) and by evaluating the risk factors and identifying predictive biomarker for the development of HCC longer-term (PearL study, N=3000 participants).

Host/viral genetic predisposition to HCC (Work package 2) will investigate the host/viral genetic predisposition to HCC using genome-wide sequencing to look for DNA sequence variations (Single Nucleotides Polymorphisms; SNPs) that are known (as well as yet not known) to be associated with HCC risk. 

Microenvironmental determinants of malignant transformation (Work package 3) will define the microenvironmental determinants that drive malignant transformation by characterising the phenotype of cancer and non-cancer cells using transcriptomic analysis, single-copy RNA sequencing (scRNA-seq), TET-assisted pyridine borane sequencing (TAPS) and for the mapping of proteins/metabolomes in order to identify pre-cancerous HCC signatures. 

HCC-EDx with liquid biopsy-based methodologies (Work package 4) will look at lipid biopsy technologies to detect early HCC markers by identifying specific blood signatures using TET-assisted pyridine borane sequencing (TAPS) assays on cell-free DNA, identifying proteomic/metabolomic signatures using metabolic and proteomic assays and finding a potential relation between blood and metabolic/proteomic markers. In addition, the work package will verify the presence known Auto-Antibodies specific to HCC.

Multiparametric quantitative imaging for HCC-EDx (Work package 5) will investigate potential HCC-specific Imaging markers using Magnetic resonance imaging (MRI), Magnetic Resonance Elastography (MRE) and LiverMultiScan (LMS).

Data integration/analysis and future view (Work package 6) will establish a robust framework for the Data management platforms and integration (Work package 6A) and perform Integrative data analysis (Work package 6B) on the data collected from research cohorts and laboratory and imaging results.  Work package 6B will generate prediction models based on the participant data and UK primary Health Care records that are able to predict the relative risk of developing HCC for individuals within the UK population. More information can be found here.

 

Deliver work packages (see main text)