Summary: A new blood test to screen for glioblastoma brain cancer biomarkers has been developed by researchers at Penn State. The test looks for elevated levels of IL13Rα2, an antigen receptor derived from glioblastoma tumors.
Source: Penn State
Glioblastoma (GBM) is the most common and deadliest type of brain cancer with a five-year survival rate of only 5%.
Researchers at Penn State College of Medicine have identified a biomarker that can be used in blood tests to diagnose GBM, track its progression and guide treatment.
The researchers said such a noninvasive liquid biopsy for GBM could help patients get the care they need faster.
“Patients normally receive images, such as MRIs or CT scans, to diagnose and monitor brain tumor progression, but it can be difficult for doctors to tell from these scans if the patient is improving or getting worse. makes it worse because they don’t provide details at the cellular or molecular level,” said Vladimir Khristov, graduate and medical student, Penn State.
“That’s why we need an additional diagnostic test to help doctors determine whether tumors are responding to treatment and shrinking, or getting worse and needing further treatment.”
Indeed, added Brad Zacharia, associate professor of neurosurgery and otolaryngology, Penn State, a liquid biopsy for glioblastoma could be invaluable for patients suffering from this devastating tumor.
“A liquid biopsy can aid in diagnosis and, more importantly, provide a better understanding of tumor response to treatment in a way that is lacking with our current technologies,” he said.
The team studied a certain antigen receptor, called interleukin-13 receptor α2 (IL13Rα2), which is known to be elevated in the tumor tissue of more than 75% of patients with GBM.
“Although it is significantly overexpressed in tumor tissues, no studies have explored the diagnostic and prognostic potential of IL13Rα2 circulating in patient biofluids,” said James Connor, Distinguished Professor of Neuroscience and Anatomy, Penn State.
To investigate the utility of IL13Rα2 as a biomarker of GBM, researchers examined tumor tissue and blood plasma from 79 patients with primary GBM, as well as blood plasma from 23 control patients, from two systems of different health. Control patients had primary diagnoses of spinal stenosis or arteriovenous malformation, but had no malignancy or chronic inflammation.
In the patients’ plasma, the researchers looked specifically for extracellular vesicles, which are small particles released by cells and transport material from those cells. They found that patients with GBM had significantly elevated levels of IL13Rα2 in their blood plasma compared to control patients and that IL13Rα2 was likely concentrated on extracellular vesicles derived from tumor cells.
They also found that these IL13Rα2 levels in blood plasma correlated with IL13Rα2 levels in the patients’ tumors.
Their findings were published in the Journal of Neuro-Oncology.
“The fact that we documented IL13Rα2 on tumor-derived extracellular vesicles and observed a correlation between plasma and tumor IL13Rα2 levels suggests that plasma IL13Rα2 indeed derives from GBM tumors,” Khristov said.
“This is important because previously it was difficult to tell if IL13Rα2 in plasma came from tumors or if it came from the body’s response to tumors. Our findings suggest that IL13Rα2 has utility as a biomarker for glioblastoma.
Connor noted that the finding is particularly significant given that IL13Rα2 has been shown to have a patchy distribution in GBM tumors, raising the question of whether a needle biopsy or a small tissue sample tumor is representative of the tumor as a whole.
“Testing circulating IL13Rα2 in plasma can provide an even better picture of the presence and extent of GBM than a tumor sample,” Connor said. Additionally, he said, “the tumor-specific nature of IL13Rα2 implies that it can be used for tumor-targeted therapies without affecting outside tissues.”
Interestingly, the team found that high levels of IL13Rα2 in plasma and tumors predicted longer overall survival. In fact, patients with high levels of plasma IL13Rα2 had a median overall survival 6.5 months longer than patients with low levels.
“It seems counterintuitive that high levels of plasma IL13Rα confer a survival advantage since their presence indicates tumor and ultimately we don’t know why this is the case,” Khristov said.
“However, there is evidence that an increase in IL13Rα2 correlates with an increase in fibrosis in the tumor, indicating tissue healing. It is important for patients to know if they can have this benefit from survival or not.
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Zacharia noted that this work, and that of many other studies, relies on biological samples, such as blood, tumor tissue and cerebrospinal fluid, from patients.
“Their generous and selfless donations of these specimens to the Penn State Neuroscience Institute Biorepository make this work possible,” he said, “and we are eternally grateful to the patients and their families.”
About this brain cancer research news
Author: Press office
Source: Penn State
Contact: Press Office – State of Pennsylvania
Picture: Image is in public domain
Original research: Access closed.
“Plasma IL13Rα2 as a new liquid biopsy biomarker for glioblastoma” by Vladimir Khristov et al. Journal of Neuro-Oncology
Abstract
Plasma IL13Rα2 as a new liquid biopsy biomarker for glioblastoma
Aim
Glioblastoma (GBM) is the most common and deadliest brain tumor with relentless and rapid disease progression. The standard of care for GBM is surgical excision followed by radiation therapy with concomitant and adjuvant chemotherapy centered on temozolomide (TMZ). Treatment failure and resistance are the rule and despite advances in imaging technology, early detection of treatment failure or impending resistance remains a challenge. There is an urgent and unmet need in clinical practice for minimally invasive diagnostic tools to enable rapid understanding of disease progression and response to treatment. Here, we aim to address this clinical need by taking advantage of a unique feature of GBM: the overexpression of the α2 variant of the IL-13 receptor in more than 75% of GBM tumors.
Methods
In this study, we examined patients with primary GBM from Penn State and Cleveland Clinic compared to healthy controls.
Results
IL13Rα2 was detectable in plasma of GBM patients by ELISA, but detection could be optimized by PEG precipitation to enrich extracellular vesicles (EVs). Patients with GBM had elevated levels of plasma IL13Rα2, which correlated with levels of this receptor in tumor tissue. Elevated plasma levels of IL13Rα2 predicted longer overall survival (OS) (19.8 versus 13.2 months). Similarly, detection of IL13Rα2+ cells in tumor tissue also predicted longer OS (22.1 vs. 12.2 months).
Conclusion
These results strongly suggest that expression of the IL13Rα2 receptor confers a survival advantage in patients with GBM, which can be determined by minimally invasive liquid biopsy. Detection of plasma IL13Rα2 can also be used to select patients with GBM for targeted tumor therapy.