Early noninvasive diagnosis and staging of liver cancers
Our research group focuses on the use of non-invasive diagnostics to identify liver disease and patients who may benefit most from liver surgery. Small blood draw followed by biotechnological analysis are used to screen patients or to complete conventional diagnostics.

Hepatocellular carcinoma (HCC) represents the most common primary hepatic malignancy and represents the second leading cause of cancer-related deaths worldwide. The incidence increased by 80% over the past 20-30 years. With a median life expectancy of up to 20 months, the outcome is generally poor despite advances in diagnosis and therapy. HCC is associated with liver cirrhosis in more than 80% of the cases. There are geographic differences due to the main risk factors. While in Asia and Africa hepatitis B infection is predominant, in Western nations it is infections with hepatitis C virus and ethyltoxic liver cirrhosis. Clinically, HCC usually remains inapparent, sometimes presenting with nonspecific signs such as pain in the right upper abdomen or unwanted weight loss. Thus, detection of HCC and other liver carcinomas remain challenging and are often too late in advanced stages. Early diagnosis would help to initiate proper diagnosis and therapy with curative intent. Therefore, our group focuses on non-invasive diagnosis of liver cancer and liver dysfunction to improve patient care.

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Figure 1: Concept of liquid biopsy exemplified by liver-specific extracellular particles.


The concept of liquid biopsy can be described as non-invasive alternative to the classic biopsy, in which information about the condition of an organ can be derived from a blood sample and the molecules circulating in it (Figure 1). We have recently explored the importance of liver-specific extracellular particle population. Liver dysfunction and acute cellular rejection subsequent liver transplantation is diagnosed by liver biopsy and concomitant histological analysis, representing the gold standard in clinical practice. Yet, liver biopsies are invasive, costly, time intensive and require expert knowledge. We are able to diagnose acute cellular rejection non-invasively. A novel extracellular particle populations in samples were identified using visualization of t-distributed stochastic neighbor embedding (viSNE) maps and self-organizing maps (FlowSOM) algorithms. It was found that the ASGR1+ CD130+ annexin V+ particles exhibited the highest accuracy for predicting acute cellular rejection (Figure 2). In addition to the analysis of extracellular particles, our group is engaged in metabolomics analyses and analyses of the phenotypic properties of immune cells to open up new diagnostic applications (Figure 3).

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Figure 2: Clustering and color coding with FlowSOM and viSNE for identifying EP subpopulations via density plots. t-SNE (t-distributed stochastic neighbor embedding), an unsupervised nonlinear dimensionality reduction algorithm, was used to fit six-dimensional data into two dimensions. All clusters were created via FlowSOM analysis. The arrow indicates the novel ASGR1+CD130+AnnV+ EP population. (Kaan et al. 2021)




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Figure 3: cfDNA analysed according to survivors and non-survivors (1-year follow-up). Patients with cfDNAlow displayed a superior 1-year survival rate; the 1-year survival rate with cfDNAlow (90 bp) was 95%, compared with 66% for cfDNAhigh (p = 0.01). Mann–Whitney U test; Log-rank test (for survival); * p < 0.05; ** p < 0.01. (Krenzien et al. 2020).




Our Team

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Principal Investigator

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Dr. rer. medic Philipp Brunnbauer

Student

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