Researchers at Emory University's Winship Cancer Institute have identified the first cerebrospinal spinal fluid (CSF) protein fingerprint that can identify low- and high-grade astrocytomas--a type of brain tumors that were once thought to arise from small, star-shaped cells in the brain called astrocytes.
The finding could lead to potential new tools for the detection, diagnosis, prognosis and follow-up after therapy of these deadly brain tumors. The researchers also found that some of these protein biomarkers may play a critical role in the development and progression of astrocytomas. This knowledge could lead them to identify targets for new therapies.
The study, "Proteomic Identification of Biomarkers in the Cerebrospinal Fluid of Astrocytoma Patients," is published online in the Journal of Proteome Research and will be published in the February issue.
CSF is a liquid that surrounds and protects the brain and acts as a reservoir, which can be sampled for analysis of proteins secreted by tumors in the central nervous system. Using two different proteomic techniques, the researchers analyzed the protein profiles of CSF from 60 patients with grades II, III and IV astrocytomas; with non-astrocytic brain tumors; and from non-tumoral control samples.
"We examined the CSF as a potential reservoir of proteins secreted during brain tumor development. We wanted to determine whether CSF from specific types and grades of brain tumors have a characteristic profile of important protein biomarkers or might give us insights into the process of brain tumor formation," says Erwin Van Meir, PhD, professor of neurosurgery and hematology/oncology at Emory's Winship Cancer Institute and lead author of the study. "And what we found were critical differences in the CSF protein expression profiles of patients with and without tumors. CSF from patients with brain tumors had a specific signature, akin to a fingerprint."
Because the CSF is adjacent to astrocytomas and can be sampled through a spinal tap, the CSF can play an important role in tumor detection. While the brain may be inaccessible without neurosurgery, the CSF can deliver clues as to what is happening inside. However, despite the fact that changes in the CSF's protein composition can be a sensitive indicator of tumor development, the clinical application of tracking these changes has been limited due to the lack of effective techniques.
"There is a pressing need for both a better understanding of brain tumor formation and the development of reliable biomarkers of malignancies," says Dr. Van Meir. "Patients with highly malignant brain tumors, of grade IV, oftentimes have a life expectancy of less than one year even after surgery, chemotherapy and radiation therapy. This highlights the need for developing better means to track brain tumors and develop novel therapies to neutralize them. The rapid development of novel proteomic techniques will accelerate this pressing goal."
The grade of a tumor reflects the level of abnormality its cells exhibit, how quickly the tumor is likely to grow and spread, and is a predictor of patient outcome. Low-grade tumors are slow growing and show little abnormality, whereas high-grade tumors are highly abnormal and grow and spread quickly, making treatment more difficult.
Other authors of the study include Fatima W. Khwaja, PhD, Matthew S. Reed, PhD, Jeffrey J. Olson, MD, Brian J. Schmotzer, MS and Jan Pohl, PhD, Emory University; G. Yancey Gillespie, PhD, University of Alabama at Birmingham; Abhijit Guha, MD, Arthur and Sonia Labatts Brain Tumor Center; Morris D. Groves, MD, M. D. Anderson Cancer Center; and Santosh Kesari, MD, PhD, Dana Farber Cancer Institute.
The authors would like to thank the patients at Emory University Hospital; the University of Alabama at Birmingham; the University of Toronto, Ontario; MD Anderson Cancer Center in Houston; and the Dana Farber Cancer Institute in Boston who generously provided their samples to advance scientific research.