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Influence of HMGA-genes on the development and progression of human SCCHN

Description

The project investigates the prognostic value of HMGA-expression on survival and progression of squamous cell carcinoma of the head and neck (SCCHN). The SCCHN tumour entity is the entity with the greatest increase in incidence among males through the 90s. HMGA-proteins, which are overexpressed in many tumour tissues, are commonly only weakly expressed in healthy adult cells. The expression of the HMGA-genes is strongly controlled by micro-RNAs which bind to the 3’UTRs. Previous studies indicate that the overexpression of HMGA-proteins in tumour tissue correlates with a worsened prognosis of the patients (e.g. by interfering with the regulatory p53 network). Biologic material collected for a previous hospital-based case-control study gave us the possibility to investigate the tumourigenic re-expression of HMGA-genes and the role of genetic gene variations on re-expression of HMGA-genes and tumour survival. The possible influence of exogenous noxae such as tobacco or alcohol consumption on HMGA-expression and disease risk and their possible interplay with a genetic predisposition was a secondary research question. High HMGA2 expression in tumor tissues of HNSCC patients was significantly correlated with negative HPV status (p=0.01), and associated with shorter overall survival time. In Cox regression modelling, HMGA2 expression yielded a risk increase for overall and tumor-specific death in subsets of HNSCC patients.
The understanding of these mechanisms could offer new strategies for cancer treatment. For example, HMGA-expression in tumour tissue could be reduced or HMGA-proteins could be inactivated to reactivate p53-induced apoptosis of malign cells.

Funding period

Begin:   May 2010
End:   April 2014

Sponsor

  • German Research Foundation

Contact

Dr. rer. nat. Kathrin Günther

Cooperation

  • Prof. Dr. Wolfgang Bergler (Chefarzt der Klinik für Hals-, Nasen-, Ohrenheilkunde, Kopf-, Hals- und plastische Gesichtschirurgie am St. Josephstift, Bremen)
  • Prof. Dr. Jörn Bullerdiek (Universität Bremen, Zentrum für Humangenetik (ZHG))
  • Prof. Dr. Ercole Di Martino (Chefarzt der Klinik für Hals-, Nasen- und Ohrenheilkunde und Plastische Kopf- und Halschirurgie am Diakonie-Krankenhaus, Bremen)
  • PD Dr. Burkhard Helmke (Chefarzt der Pathologie der Elbe Kliniken Stade-Buxtehude GmbH, Stade)
  • Prof. Dr. Andreas Naumann (Chefarzt der Hals-Nasen-Ohrenklinik, plastische Operationen am Klinikum Bremen-Mitte)
  • Dr. Rolf Nimzyk (Universität Bremen, Zentrum für Humangenetik (ZHG))

Selected project-related publications

    Articles with peer-review

  • Günther K, Foraita R, Friemel J, Günther F, Bullerdiek J, Nimzyk R, Markowski DN, Behrens T, Ahrens W. The stem cell factor HMGA2 is expressed in non-HPV-associated head and neck squamous cell carcinoma and predicts patient survival of distinct subsites. Cancer Epidemiology, Biomarkers & Prevention. 2017;26(2):197-205.
    https://doi.org/10.1158/1055-9965.EPI-16-0492
  • Friemel J, Foraita R, Günther K, Heibeck M, Günther F, Pflüger M, Pohlabeln H, Behrens T, Bullerdiek J, Nimzyk R, Ahrens W. Pretreatment oral hygiene habits and survival of head and neck squamous cell carcinoma (HNSCC) patients. BMC Oral Health. 2016;16:33.
    https://doi.org/10.1186/s12903-016-0185-0
  • Presentations at scientific meetings/conferences

  • Foraita R, Friemel J, Günther K, Markowski DN, Hanke M, Kanz F, Behrens T, Bullerdiek J, Nimzyk R, Pigeot I, Ahrens W. Analysis of gene expression networks in head and neck squamous cell carcinoma. Congress "Health - Exploring Complexity: An Interdisciplinary Systems Approach (HEC2016)." Joint Annual Meeting of the German Society for Medical Informatics, Biometry and Epidemiology (GMDS), the German Society for Epidemiology (DGEpi), the International Epidemiological Association - European Region (IEA-EEF) and the European Federation for Medical Informatics Association (EFMI), 28 August-2 September 2016, Munich. (Abstract published in: European Journal of Epidemiology. 2016;31(Suppl.1):S55)
  • Friemel J, Foraita R, Günther K, Pflüger M, Heibeck M, Günther F, Pohlabeln H, Behrens T, Bullerdiek J, Nimzyk R, Ahrens W. Impact of oral health, dental care and mouthwash on survival of patients with head and neck squamous cell carcinoma (HNSCC). 10. Jahrestagung der Deutschen Gesellschaft für Epidemiologie (DGEpi), 30. September-2. Oktober 2015, Potsdam.
  • Günther K, Foraita R, Nimzyk R, Bullerdiek R, Ahrens R. HMGA2-Expression assoziiert mit Überlebensdauer von Patienten mit Plattenepithelkarzinomen im Kopf-Hals-Bereich (SCCHN). 9. Jahrestagung der Deutschen Gesellschaft für Epidemiologie (DGEpi), 17.-20. September 2014, Ulm.
  • Heibeck M, Günther K, Ahrens W. Überlebenswahrscheinlichkeit von Patienten mit Plattenepithel-Karzinomen im Kopf-Hals-Bereich in Abhängigkeit von medizinischen und exogenen Einflussfaktoren. 57. Jahrestagung der Deutschen Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie (GMDS), 16.-21. September 2012, Braunschweig.