Neuherberg, June 14, 2016. Scientists at the Helmholtz Zentrum München and the Ludwig Maximilians University of Munich (LMU) have developed a new method of predicting disease progression in gliobastoma patients who have undergone standard treatment. Their findings, published in the journal Oncotarget, show that four miRNAs may hold the vital clue. An application for the corresponding patent has already been filed.
Roughly one fifth of all brain tumors diagnosed by doctors are gliobastomas. This aggressive and most common type of brain tumor continues to present doctors with huge challenges. However, molecular markers could help them to make the right treatment decision. A team of researchers led by Dr. Kristian Unger, Deputy Head of the Radiation Cytogenetics Research Unit (headed by Prof. Dr. Horst Zitzelsberger) at the Helmholtz Zentrum München, and Prof. Dr. Claus Belka, Director of the Clinic and Policlinic for Radiotherapy and Radiation Oncology at the University of Munich's Grosshadern Hospital (member of the DKTK cancer research consortium), has now succeeded in identifying specific miRNAs* that could serve as biomarkers for disease progression.
miRNAs indicate a poor prognosis
In collaboration with the Institute of Neurology (Edinger Institute) at the University Hospital Frankfurt, researchers examined the composition of miRNAs in samples from 36 patients from whom tumor material had been removed during treatment, and whose subsequent course of treatment had been well documented. "We repeatedly detected four miRNAs in tumors that had a particularly poor prognosis," explains PD Dr. Karim-Maximilian Niyazi, senior physician at Grosshadern, and first author of the study. Based on their data, the scientists calculated a risk score to distinguish two patient groups who were undergoing standard treatment and whose life expectancy varied by about five months. In order to corroborate their findings, they used data obtained from a further 58 independent samples. Here, too, they found that the composition of the miRNAs altered, the worse the prospects of a successful treatment outcome were.
Patent already applied for
The scientists are confident that their observations will have more than mere theoretical implications. For this reason, they have already filed an application for the corresponding patent. "To date only few prognostic and predictive factors for glioblastoma have been identified," says research team leader Unger.** "Our method could be used to identify candidates for alternative or intensified treatment options, as it is highly unlikely that patients with a high risk score would benefit from standard therapy." Since tumor tissue would generally be removed immediately, a corresponding analysis would be relatively easy to conduct and would not require any additional time or expense, the researchers note.
Whether the miRNAs have a malignant function in the cancer cells themselves or are merely an indirect marker remains to be clarified. In initial studies, however, the scientists have shown that miRNAs could possibly even play a role in various processes of tumor development.
* miRNAs or microRNAs are a class of molecules that consist of short sequences of RNA building blocks. In contrast to protein synthesis, however, the RNA is not needed to build molecules. On the contrary, many miRNAs are capable of preventing the production of certain proteins by destroying the respective RNA blueprint. According to estimates, about 2,000 different miRNAs have been identified. However, this relatively young research area is continuing to bring new findings to light.
** To date, only few prognostic factors for glioblastoma have been identified. The most important molecular marker, methylation of the O6-methylguanine transferase (MGMT) promoter region, has been described as a positive predictor for temozolomide-based radiochemotherapy. Up to now little research has been done into miRNA changes in glioblastomas.
Niyazi, M. et al. (2016). A 4-miRNA signature predicts the therapeutic outcome of glioblastoma, Oncotarget, doi: 10.18632/oncotarget.9945
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 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.
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.
As one of Europe's leading research universities, LMU Munich is committed to the highest international standards of excellence in research and teaching. Building on its 500-year-tradition of scholarship, LMU covers a broad spectrum of disciplines, ranging from the humanities and cultural studies through law, economics and social studies to medicine and the sciences. 15 percent of LMU's 50,000 students come from abroad, originating from 130 countries worldwide. The know-how and creativity of LMU's academics form the foundation of the University's outstanding research record. This is also reflected in LMU's designation of as a "university of excellence" in the context of the Excellence Initiative, a nationwide competition to promote top-level university research. http://www.
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Scientific Contact at Helmholtz Zentrum München:
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