Glioblastoma (GBM) is the most typical and deadliest sort of mind most cancers with a five-year survival price of solely 5%. Researchers at Penn State School of Drugs have recognized a biomarker that can be utilized in blood checks to diagnose GBM, monitor its development, and information therapy. The researchers stated that such a non-invasive liquid biopsy for GBM might assist sufferers get the care they want extra rapidly.
“Sufferers usually obtain imaging, akin to MRI or CT scans, to diagnose and monitor the development of mind tumors, however it may be tough for physicians to inform from these scans if the affected person is getting higher or worse as a result of they don’t present element on the mobile or molecular degree,” stated Vladimir Khristov, graduate and medical scholar, Penn State. “That’s the reason we’d like a supplemental diagnostic take a look at to assist physicians decide if the tumors are responding to remedy and regressing, or if they’re getting worse and wish further therapy.”
Certainly, added Brad Zacharia, affiliate professor of neurosurgery and of otolaryngology, Penn State, a liquid biopsy for glioblastoma may very well be of large worth to sufferers affected by this devastating tumor.
“A liquid biopsy might facilitate prognosis and extra importantly present a greater understanding of the tumor’s response to therapy in a means that’s missing with our present applied sciences,” he stated.
The staff studied a sure antigen receptor, known as interleukin-13 receptor α2 (IL13Rα2), which is thought to be elevated within the tumor tissue of greater than 75% of GBM sufferers.
“Regardless of being considerably overexpressed in tumor tissue, no research have explored the diagnostic and prognostic potential of IL13Rα2 circulating in affected person biofluids,” stated James Connor, distinguished professor of neuroscience and anatomy, Penn State.
To research the utility of IL13Rα2 as a biomarker for GBM, the researchers examined the tumor tissue and blood plasma of 79 patients with primary GBM, along with the blood plasma of 23 control patients, from two different health systems. The control patients had primary diagnoses of either spinal stenosis or arteriovenous malformation but did not have any malignancy or chronic inflammation.
In the patients’ plasma, the researchers looked specifically at extracellular vesicles, which are small particles that are released by cells and carry 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 the IL13Rα2 was likely concentrated on extracellular vesicles derived from tumor cells. They also found that these IL13Rα2 levels in blood plasma were correlated with the IL13Rα2 levels in the patients’ tumors. Their findings were published recently in the Journal of Neuro-Oncology.
“The fact that we documented IL13Rα2 on tumor-derived extracellular vesicles and that we observed a correlation between plasma and tumor levels of IL13Rα2 suggests that plasma IL13Rα2 does indeed derive from GBM tumors,” said Khristov. “This is important because previously it was difficult to tell if the IL13Rα2 in plasma came from the tumors, or if they came from the body’s response to the tumors. Our findings suggest that IL13Rα2 does have utility as a biomarker for glioblastoma.”
Connor noted that the finding is especially significant given that IL13Rα2 has been shown to have a patchy distribution in GBM tumors, raising the question of whether a needle biopsy or small sample of tumor tissue is representative of the tumor as a whole.
“Testing for IL13Rα2 circulating in plasma may provide an even better picture of the presence and extent of GBM than a tumor sample,” said Connor. 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 elevated levels of IL13Rα2 in both plasma and tumors predicted longer overall survival. In fact, patients with high levels of plasma IL13Rα2 had a 6.5-month longer median overall survival compared to patients with low levels.
“It seems counterintuitive that high levels of plasma IL13Rα would confer a survival advantage since their presence indicates a tumor and, ultimately, we do not know why this is the case,” said Khristov. “However, there is some evidence that increased IL13Rα2 is correlated increased fibrosis in the tumor, which indicates tissue healing. It’s important for patients to know if they may have this survival advantage or not.”
Zacharia noted that this work, and that of many other studies, relies on biological specimens, such as blood, tumor tissue and spinal fluid, from patients.
“Their generous and selfless gifts of these specimens to the Penn State Neuroscience Institute Biorepository make this work possible,” he said, “and we are forever grateful to the patients and their families.”
Reference: “Plasma IL13Rα2 as a novel liquid biopsy biomarker for glioblastoma” by Vladimir Khristov, Darya Nesterova, Mara Trifoi, Taylor Clegg, Annika Daya, Thomas Barrett, Emily Tufano, Ganesh Shenoy, Bhavyata Pandya, Gela Beselia, Nataliya Smith, Oliver Mrowczynski, Brad Zacharia, Kristin Waite, Justin Lathia, Jill Barnholtz-Sloan and James Connor, 27 November 2022, Journal of Neuro-Oncology.
Other Penn State authors on the paper include Darya Nesterova, general surgery resident; Mara Trifoi, medical student; Taylor Clegg, medical student; Annika Daya, medical student; Thomas Barrett, medical student; Emily Tufano, graduate student; Ganesh Shenoy, medical student and Ph.D. student, Bhavyata Pandya, graduate student; Nataliya Smith, human research technologist; Oliver Mrowczynski, neurosurgery resident; Brad Zacharia, associate professor of neurosurgery and otolaryngology; Gela Beselia, postdoctoral fellow, Albany Medical College; Kristin Waite, staff scientist, National Cancer Institute; Justin Lathia, professor of molecular medicine, Case Western Reserve University; Jill Barnholtz-Sloan, senior investigator, National Cancer Institute.