Molecular Diagnostics in Early Detection of Cancer
Early detection of tumors represents a widely consented strategy to decrease
cancer mortality and morbidity. Currently, early detection is limited to few tumor entities and employs techniques like physical examination (skin), laboratory analyses (prostate) or endoscopy (colon). The advent of novel molecular techniques such as targeted sequencing approaches or antibody-based proteomics and its application in liquid biopsies substantially enhanced sensitivity and specificity of screening. This core research program aims to identify diagnostic biomarkers, which allow the identification of patients at relevant risk of cancer development or relapse.
- We take advantage of three population-based cohort studies with almost 20,000 participants and sequential follow-up:
• The Gutenberg Health Study (GHS) is an interdisciplinary, population-representative study, which provides a biodatabase of over 15,000 study participants. The prospective GHS combines comprehensive deep (sub) clinical phenotyping with numerous molecular data levels (e.g. genetics, targeted proteomics, microbiome). During long-term follow-up, we observed more than 1,800 incident cancer cases.
• The MyoVasc Study (N=3,289; NCT04064450) has been established as internationally unique biodatabase with sequential molecular and deep clinical phenotyping (biannual investigations; study duration 8 years) of individuals with heart failure. Omics data (e.g. genetics, whole blood gene expression, targeted proteomics) in conjunction with biobanking are available. Hitherto, more than 100 incident cancer cases have already occurred in this high-risk population since start of the study in January 2013.
• The VTEval Project (N=1,260; NCT02156401) consists of three observational, prospective cohort studies on venous thromboembolism. Each study participant is followed-up over a five-year time period. Follow-up investigations include sequential clinical examination, biobanking, molecular profiling (e.g. targeted proteomics, platelet function testing, genetics), and assessment of cancer status (currently N=320 cancer patients).
- Cancer and cardiovascular disease are known to share risk factors (e.g. smoking, obesity, and systemic inflammation), but also mutually predispose for disease development. The established bio-databases of Preventive Cardiology / Clinical Epidemiology and Systems Medicine provide the unique opportunity to investigate the interplay of cancer with the cardiovascular system in various settings ranging from the general population (GHS) to specific disease entities (Panova-Noeva M., et al. Thromb Res. 2016). The research group has established a pipeline for systems-oriented biomedical research to analyze the diverse set of sequential multi-omics data using state-of-the-art methods from biostatistics and machine learning.
- Within the HCC program, the largest translational study program focusing on metabolic liver disease in Germany has been established. The program includes the identification and validation of biomarkers for non-alcoholic steatohepatitis (NASH) and nonalcoholic fatty liver disease (NAFLD) or the LIFT-off initiative, which investigates lifestyle intervention to improve hepatic fibrosis in NAFLD. In addition, several preclinical models have been established enabling the analysis of sequential HCC development (Farrell G., et al. Hepatology. 2019) and lifestyle interventions (Huber Y., et al. Cell Death Dis. 2017; Gehrke N., et al. Sci Rep. 2019).
- Early detection followed by early intervention (“adjuvant” therapy) for patients at risk represent prerequisites to ensure patient cure and survival. Patients with detectable MRD after curative therapy are at high risk for relapse. To allow detection of circulating tumor DNA (ctDNA), TRON has developed a highly sensitive and specific NGS-based method.
The sequential analysis of biomaterial from individuals who participate in cohort- studies and develop any kind of malignant disease during follow-up will provide unique information with respect to tumorigenesis and identification of predictive markers. Systems-oriented biomedical research to analyze the diverse set of sequential multi-omics data using state-of-the-art methods from biostatistics and machine learning will be promoted. The new developed highly sensitive and specific NGS-based technique from TRON will be used to identify ctDNA in patients with stage II/III colorectal cancer after adjuvant chemotherapy. In addition, minimal residual disease (MRD) positivity will be coupled to (pseudo)adjuvant, individualized immunogenic RNA vaccine intervention within a proof-of-concept clinical trial within the regional UCT Mainz network.
Department of Internal Medicine I - Gastroenterology, Hepatology, Nephrology, Rheumatology, Infection, Endocrinology, and Metabolic Disorders:
Center for Thrombosis and Hemostasis Mainz:
Most significant publications since 2015
- Gehrke, N., Hövelmeyer, N., Waisman, A., Straub, B.K., Weinmann-Menke, J., Wörns, M.A., Galle, P.R., Schattenberg, J.M. 2018. Hepatocyte-specific deletion of IL1-RI attenuates liver injury by blocking IL-1 driven autoinflammation. J Hepatol. 68(5):986-995.
- Dörsam, B., Seiwert, N., Foersch, S., Stroh, S., Nagel, G., Begaliew, D., Diehl, E., Kraus, A., McKeague, M., Minneker, V., Roukos, V., Reißig, S., Waisman, A., Moehler, M., Stier, A., Mangerich, A., Dantzer, F., Kaina, B., Fahrer, J. 2018. PARP-1 protects against colorectal tumor induction, but promotes inflammation-driven colorectal tumor progression. Proc Natl Acad Sci U S A. 115(17):E4061-E4070.
- Faber, J., Wingerter, A., Henninger, N., Eckerle, S., Münzel, T., Lackner, K.J., Beutel, M.E., Blettner, M., Rathmann, W., Peters, A., Meisinger, C., Linkohr, B., Neuhauser, H., Kaatsch, P., Spix, C., Schneider, A., Merzenich, H., Panova-Noeva, M., Prochaska, J.H., Wild, P.S. 2018. Burden of cardiovascular risk factors and cardiovascular disease in childhood cancer survivors: data from the German CVSS-study. Eur Heart J. 39(17):1555-1562.
- Panova-Noeva, M., Schulz, A., Arnold, N., Hermanns, M.I., Prochaska, J.H., Laubert-Reh, D., Spronk, H.M., Blettner, M., Beutel, M., Pfeiffer, N., Münzel, T., Lackner, K.J., Ten Cate, H., Wild, P.S. 2018. Coagulation and inflammation in long-term cancer survivors: results from the adult population. J Thromb Haemost. 16(4):699-708.
- Schuppan, D., Surabattula, R., Wang, X.Y. 2018. Determinants of fibrosis progression and regression in NASH. J Hepatol. 68(2):238-250.