Speaker
Ms
Isolde Summerer
(Helmholtz Zentrum Muenchen)
Description
MicroRNAs (miRNAs) are present in stable extracellular forms in body fluids such as liquor or blood plasma. Changes in the levels of circulating miRNAs of cancer patients are associated with malignant progression and have proven useful for the prediction of therapy responses. This study is intended to investigate if therapeutic irradiation induces changes in the plasma miRNA profiles of head and neck cancer patients. The aim is to establish plasma miRNAs as non-invasive biomarkers to predict tumor response in radiation therapy.
MiRNA expression profiles of blood plasma samples from 7 head and neck cancer patients were analyzed before and after local irradiation in 2 fractions of 2Gy each. Plasma samples of an age and sex-matched collective of 6 healthy donors were investigated in parallel. Real-time PCR with TaqMan™ low-density miRNA-cards allowed quantification of a pool of 377 miRNAs in the plasma.
CT-values were normalized to the mean value of all detected (Ct ≤ 35.5) miRNAs in each case. Changes in miRNA-quantity after irradiation were calculated via ∆∆-CT-method and student’s t-test was applied to determine differentially expressed miRNAs. Single Primer Assays were performed for selected miRNAs in order to validate the changes.
Out of 377 investigated miRNAs approximately 100 were detected in patient plasma. After exposure on average 15 miRNAs showed increased expression, while 24 miRNAs showed lower expression levels. These include “switch on” and “switch off” miRNAs which are exclusively detected with or without irradiation. Remarkably, 26 miRNAs were identified as responding to irradiation in at least 4 out of 7 patients.
Additionally, tumor specific miRNA signatures were identified by comparative cluster analysis of the miRNA profiles of nonirradiated patient plasma and miRNA profiles of plasma from healthy donors.
In this pilot study we identified changes of the miRNA-levels in the plasma of head and neck cancer patients after therapeutic irradiation. Furthermore we detected miRNA signatures that are specific for head and neck cancer patients. A correlation of the obtained results with clinical outcome data and a validation in further patients is in progress. The quantification of radiation-responsive miRNAs in blood plasma may provide a minimally invasive way to predict the radiation therapy response of tumor patients, thus potentially leading to a more individualized treatment in the future.
Primary author
Ms
Isolde Summerer
(Helmholtz Zentrum Muenchen)
Co-authors
Dr
Anne Kraemer
(Helmholtz Zentrum Muenchen)
Prof.
Horst Zitzelsberger
(Helmholtz Zentrum Muenchen)
Dr
Maximilian Niyazi
(Ludwig Maximilians Universitaet Muenchen)
Prof.
Michael Atkinson
(Helmholtz Zentrum Muenchen)
Dr
Simone Moertl
(Helmholtz Zentrum Muenchen)
