Researchers at Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine have discovered a peripheral biomarker in human blood serum that can be used to detect the presence and progress of glioblastoma brain tumors before and after treatment.
Their findings were published in an article, “Serum long noncoding RNA HOTAIR as a novel diagnostic and prognostic biomarker in glioblastoma multiforme,” in the journal Molecular Cancer on March 20.
Glioblastoma multiforme (GBM) is the most common and aggressive malignant adult primary brain tumor. Despite surgical resection followed by radiotherapy and chemotherapy, the median survival rate is approximately 14 months. Although experimental therapies for GBM are in clinical trials, there is an urgent need for a peripheral GBM biomarker for measuring treatment response.
“We discovered a novel biomarker for GBM,” said the article’s corresponding author, Nagi G. Ayad, Ph.D., associate professor of psychiatry and behavioral sciences. “A peripheral biomarker is a way of detecting a sign of cancer progression in the blood. We developed a way to detect an RNA termed HOTAIR in the serum of glioblastoma patients that was not present in the serum of patients who do not have this disease.”
Ayad and Sylvester colleagues Ricardo J. Komotar, M.D., associate professor of neurological surgery, Michael E. Ivan, M.D., assistant professor of neurological surgery, and Claes Wahlestedt, M.D., Ph.D., professor of psychiatry and behavioral sciences, found HOTAIR in pieces of tumor cells, called exosomes, in the serum from GBM patients. They also monitored the patients and determined the levels of HOTAIR in their serum before and after surgery to remove the tumor, finding that HOTAIR levels decrease after surgery. They postulate that, as the tumor is removed, there are fewer exosomes in circulation, and therefore less HOTAIR to be detected in serum.
“Our prior research showed that HOTAIR levels are controlled by an epigenetic regulator named BRD4,” said Ayad. “BRD4 inhibitors are in clinical trials for various cancers, including GBM. Our new findings suggest that the levels of HOTAIR can be monitored during clinical trials to determine whether the BRD4 inhibitors are effective. HOTAIR levels can also be monitored to determine when, or whether, tumors return.”
The next step will be collaboration with the University of Miami Brain Tumor Initiative researchers to determine whether HOTAIR levels in GBM patients can be measured during one year of treatment. The researchers have an approved IRB to measure HOTAIR in GBM patients during treatment to determine when progression occurs. They also hope to conduct similar research with pediatric brain tumor patients.
Through another collaboration, with Stephan Schürer, Ph.D., associate professor of molecular and cellular pharmacology, and lead cheminformatics scientist at the University of Miami Center for Computational Science, they have also developed a novel platform to identify a patient-specific approach for drug combinations to treat GBM. Their plan is to work with the University of Miami Brain Tumor Initiative to test FDA-approved compound combinations in clinical trials to determine their effect on HOTAIR levels.
“It is clear that an integrated basic science and translational approach will be required to develop therapies and biomarkers for GBM,” said Ayad.
The research is supported by funding from the Epigenetics Program at Sylvester Comprehensive Cancer Center.