Researchers at two German research facilities, the Ludwig Maximilians University of Munich (LMU) and Helmholtz Zentrum München have reported a new way to predict disease progression in gliobastoma patients who underwent standard treatment. Their study
, published in Oncotarget, has shown that four microRNAs (miRNAs) might be the critical reporters. Measuring the levels of those miRNAs enabled the team to predict how good or bad the prognosis was for the patient. A patent application for this work has even been filed already.
Collaborating with the Institute of Neurology at the University Hospital of Frankfurt, researchers were able to directly examine tumor samples from 36 patients who had well-documented health and treatment histories. "We repeatedly detected four miRNAs in tumors that had a particularly poor prognosis," says Dr. Karim-Maximilian Niyazi, a physician at the hospital at LUM and first author of the study.
miRNAs are molecules made up of short sequences of RNA. They seem to work in a variety of ways as a regulator; they turn off genes by disrupting the RNA level, by reducing stability or inhibiting translation. An estimated 2,000 different miRNAs have been identified so far in plants, animals and even in some viruses.
Glioblastomas are considered highly malignant brain tumors because of the speed with which they reproduce as well as having an extensive blood vessel support network. They are the most common type of brain tumor, with an unclear cause and very few biomarkers that indicate their presence. Glioblastomas have also been shown to have miRNA ‘expression signatures’.
The scientists were able to use their data on miRNA expression to create a risk score for patients, and that score separated the patients into two distinct groups, different from the other in their prognosis. One group had a survival prediction of 10 months, the other group was given 15 months.
The findings were then corroborated using an additional 58 patient samples. Using their computational methods to calculate risk scores, they were able to confirm the predictive value with the new cohort.
Looking at where those miRNAs might be exerting their activity, they saw effects on a pathways like axon guidance, immune response, and membrane transport, all of which are well known to participate in tumorigenesis. One miRNA is specifically related to tumor suppression, and that miRNA was also expressed at a higher level in patients with a more favorable outcome.
The researchers are fairly confident in the use of miRNAs to predict severity of disease in patients with glioblastomas following chemotherapy or surgery. They also note that this could be another small advance for the field of personalized medicine, as those with good predictions could be served by typical therapy, while patients with a poor prognosis might be put on a more aggressive regimen.
For a detailed explanation of how microRNAs work, check out the video below.