Research Networks

Early detection and prevention of liver cancer

Systems medicine research network for the early detection and prevention of liver cancer

About

Our Mission

Liver Systems Medicine Cancer - LiSyM-Cancer - is a multidisciplinary research network funded within the Federal Ministry of Education and Research (German: Bundesministerium für Bildung und Forschung, BMBF) program "Funding of a Systems Medicine Research Network for the Early Detection and Prevention of Liver Cancer" within the Framework of the National Decade Against Cancer. The funding period is July 2021 until July 2024.

The LiSyM-Cancer research network builds on the achievements of the previous network LiSyM (funding period 2016 to 2020) and is extending the research focus to liver cancer.

In the LiSyM-Cancer network, molecular and cell biologists, clinical researchers and experts in mathematical modeling are jointly conducting research to investigate the development of liver cancer from pre-existing conditions such as non-alcoholic fatty liver or liver cirrhosis. The aim of the joint project is to identify relevant biomarkers to diagnose and prevent hepatocellular carcinoma (HCC) at early stages.

Synergistic work programme in LiSyM-Cancer

LiSyM-Cancer comprises three subprojects - SMART-NAFLD, C-TIP-HCC and DEEP-HCC and the Programme and Data Management. These projects use an integrative systems medicine approach in which liver cell communication, metabolism and signal transduction as well as the dynamics of the different liver cell populations and the composition of the extracellular matrix are examined. High-standard multi- and spatial-OMICS and imaging methods are applied. Based on quantitative data, mathematicians and bioinformaticians develop models to enable the early detection of alterations (tipping points) facilitating liver cancer development. Although most liver cancers develop based on cirrhosis (tipping point 2), due to the rapid increase of overweight and obese patients with NAFLD, the first tipping point is becoming increasingly important.

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The three projects in LiSyM-Cancer: SMART-NAFLD characterises the transition from NAFLD directly to HCC (tipping point 1), C-TIP-HCC investigates the transition from liver cirrhosis to HCC (tipping point 2) and DEEP-HCC provides an multi-dimensional characterisation of early HCC.

Subprojects

SMART-NAFLD

SMART-NAFLD focuses on alterations in metabolism and signal transduction that favor disease progression to liver cancer. The project aims to identify alarm signatures in the blood of patients with fatty liver diseases without cirrhosis. This will facilitate to develop model-based trajectories for individual patients to evaluate the closeness to the tipping point towards liver cancer (tipping point 1).

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C-TIP-HCC

C-TIP-HCC employs multiscale modeling to address structural and compositional changes in the extracellular matrix, and differences in cellular phenotypes in cirrhotic nodules. This facilitates the discrimination of the tissue in compensated cirrhosis across a tipping point towards liver cancer formation (tipping point 2). Aim of the modeling is to predict strategies to prevent or slow down disease progression from cirrhosis to liver cancer.

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DEEP-HCC

DEEP-HCC focuses on early liver cancer and provides an unprecedented deep multi-dimensional functional and spatial characterization, with tissue-to-single cell precision. A comprehensive data set will be generated consisting of 3D digital tissue reconstruction, spatial transcriptomics, epigenetics, lipidomics, pseudotime-ordered somatic mutations and personalized complex liver cancer organoids. This unique convergence of datasets will be integrated within a comprehensive metabolic/signaling-, spatio-temporal- and stochastic modelling workflow, to reveal emergent multimodal liver cancer signatures.

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LiSyM-Cancer furthermore addresses the following questions:

  1. What are the similarities and differences of the HCCs arising in patients with fatty liver disease in the absence of cirrhosis versus those that develop in patients with liver cirrhosis?
  2. Which factors or mechanisms explain that men are significantly more likely to develop liver cancer than women?
  3. Which components in the blood reflect a crossing of the tipping points for liver cancer development and could be used as biomarkers for early detection?
  4. Which parameters of tipping point exceedance could serve as target structures that prevent or significantly delay the development of HCC?

Programme and Data Management

The essential goal of the Programme Directorate and Management is to enable and support cross-network consortial cooperation and to mediate synergies between the consortia so that the milestones of the individual projects and the entire network can be successfully achieved. A trustworthy exchange of data is indispensable and includes compliance with data protection regulations which is facilitated and organised by a central, super-ordinate data management system. For optimal collaboration the programme management and data management are combined.

The data architecture uses the following systems: FAIRDOM SEEK for sharing scientific data and publications, the open source NextCloud for fast sharing of semi-structured big data, OMERO for sharing image data, openBIS for near-lab sharing of data and metadata and REDCap for patient data.

News / Events

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Young Scientists Retreat


Meeting of the students and PostDocs in Hofgeismar.

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LiSyM-Cancer Status Seminar 2023


Annual Status seminar of the whole consortium

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