microRNAs Predict Recurrence Risk of Head and Neck Tumors

Squamous cell carcinomas of the head and neck (HNSCC) are usually only diagnosed at an advanced stage and thus have a relatively poor prognosis. One cause may be human papillomavirus (HPV), but the main cause is tobacco smoking and excessive consumption of high-percentage alcohol.

“While the virally induced tumors can be treated relatively well, the other head and neck tumors have a rather poor prognosis,” said Professor Claus Belka, MD, head of the Clinical Cooperation Group (CCG) 'Personalized Radiotherapy in Head and Neck Cancer'. The CCG comprises scientists from Helmholtz Zentrum München and LMU and is closely associated with the DKTK.

“In this study, we investigated how molecular markers can be used to define subgroups that undergo a different course of disease after radiation chemotherapy,” Belka said. This could offer an opportunity for personalized treatment. “The Research Unit Radiation Cytogenetics at Helmholtz Zentrum München, headed by Professor Horst Zitzelsberger, offers optimal detection methods and expertise for the identification of such molecular markers, which allow the stratification of patients.”

Patient data provide an approach to personalized therapy

To investigate this question, the researchers examined cancer tissues from two independent tissue sample collections: Specifically, it was a multicenter patient collective of the DKTK Radiation Oncology Group (DKTK-ROG; coordination of the miRNA study Prof. Michael Henke) and a monocentric patient collective from the LMU Clinic for Radiotherapy and Radiation Oncology (head: Prof. Belka). In the analysis, the researchers focused on miRNAs: tiny molecules that influence the expression of numerous (in part cancer-relevant) genes.

“Working with our colleagues enabled us to study a total of 162 samples from patients with HPV-negative head and neck cancer,” said Dr. Julia Hess. She shares the first authorship with Dr. Kristian Unger. Both are heading a working group in the Research Unit Radiation Cytogenetics. Out of all of the miRNAs, the researchers were able to identify five miRNAs whose expression predicted the course of the disease and the risk of recurrence. “In combination with other clinical data, this five miRNA signature allows the definition of four groups with different prognoses,” Unger added.

“Such molecular markers are the first prerequisite for personalized treatment approaches in HPV-negative head and neck tumors,” said Belka. “If these figures can be confirmed on a large scale, personalized adjustments in therapy intensity could be derived from them in the future.” For example, it would be conceivable to reduce the intensity of therapy in patients with a low risk of recurrence or to increase it in high-risk patients. In addition, it is now possible to search for the genes that are influenced by the five miRNAs and find out whether they represent worthwhile target structures for therapy.

Further Information

Background:
In 2016, the scientists had already identified a miRNA signature that makes it easier to estimate the course of the disease in brain tumors. miRNAs or microRNAs are a class of molecules consisting of short sequences of RNA building blocks. Unlike protein synthesis, however, RNA is not needed for the construction of molecules. On the contrary, many miRNAs are able to prevent the build-up of certain proteins by degrading the corresponding RNA blueprint. It is estimated that currently about 2,000 different miRNAs are known.

The Helmholtz Zentrum München, the German Research Center for Environmental Health, pursues the goal of developing personalized medical approaches for the prevention and therapy of major common diseases such as diabetes, allergies and lung diseases. To achieve this, it investigates the interaction of genetics, environmental factors and lifestyle. The Helmholtz Zentrum München is headquartered in Neuherberg in the north of Munich and has about 2,300 staff members. It is a member of the Helmholtz Association, a community of 18 scientific-technical and medical-biological research centers with a total of about 37,000 staff members. http://www.helmholtz-muenchen.de/en

The Research Unit Radiation Cytogenetics (ZYTO) investigates radiation-induced chromosome and DNA damage in cell systems and human tumours. The focus is on clarifying the mechanisms associated with radiation-induced carcinogenesis and radiation sensitivity of tumour cells. The aim of this research is to find biomarkers associated with radiation-induced tumours in order to develop personalized radiation therapy for the stratification of patients. ZYTO is a part of the Department of Radiation Sciences (DRS). http://www.helmholtz-muenchen.de/zyto

Munich University Hospital (LMU) treats around 500,000 outpatients, inpatients and semi-residential patients each year at its Großhadern and City Centre Campuses. Just over 2,000 beds are available to its 29 specialist clinics, twelve institutes and six departments, and its 49 interdisciplinary centres. Of a total of 9,450 employees, around 1,600 are doctors and 3,200 are nursing staff. Munich University Hospital has been a public-law institution since 2006. Together with the Medical Faculty of Ludwig Maximilians University, Munich University Hospital is involved in four special research areas of the German Research Foundation (SFB 684, 914, 1054, 1123), three Transregios (TRR 127, 128, 152) belonging to Clinical Research Group 809, and two Graduate Colleges belonging to the German Research Foundation (GK 1091, 1202). This is in addition to the Center for Integrated Protein Sciences (CIPSM), Munich Center of Advanced Photonics (MAP), Nanosystems Initiative Munich (NIM) and Munich Cluster for Systems Neurology (SyNergy) – all institutes of excellence – and the Graduate School of Systemic Neurosciences (GSN-LMU), the Graduate School of Quantitative Biosciences Munich (QBM) and the Graduate School Life Science Munich (LSM). http://www.klinikum.uni-muenchen.de

Contact for the media:
Department of Communication, Helmholtz Zentrum München – German Research Center for Environmental Health, Ingolstädter Landstr. 1, 85764 Neuherberg – Tel. +49 89 3187 2238 – E-mail: presse@helmholtz-muenchen.de

Dr. Julia Hess, Helmholtz Zentrum München – German Research Center for Environmental Health, Research Unit Radiation Cytogenetics, Ingolstädter Landstr. 1, 85764 Neuherberg – E-mail: julia.hess@helmholtz-muenchen.de

Hess, J. et al. (2018): A Five-MicroRNA Signature Predicts Survival and Disease Control of Patients with Head and Neck Cancer Negative for HPV-infection. Clinical Cancer Research, DOI: 10.1158/1078-0432.CCR-18-0776

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http://clincancerres.aacrjournals.org/content/early/2018/08/31/1078-0432.CCR-18-…