An FIU-led study has revealed a correlation between the presence of a protein variant and poor survival in males suffering from the deadliest form of brain cancer.
The breakthrough followed analysis of 441 patient blood samples and focuses on the translocator protein 18 kDa (TSPO) present in various types of human cells. Researchers found that patients who exhibited a variation in the structure of the protein fared worse than those who didn't. And while the variant is common among the general population, it appeared to be associated with worse outcomes in glioblastoma patients who are male.
Some 13,000 adults in the United States are diagnosed annually with glioblastoma, and males are 1.6 times more likely to be affected. The brutal disease leads to seizures, persistent headaches and personality changes in addition to impairments in speech, cognition, sight and movement. The median survival time is 12 to 14 months after diagnosis, and fewer than 7% of patients live more than five years.
The study was conducted by scientists at the Robert Stempel College of Public Health & Social Work in collaboration with Cleveland Clinic Lerner Research Institute and the National Cancer Institute. It was published in a special issue of the peer-reviewed, open access oncology journal “Cancers.”
Tomás R. Guilarte, dean of Stempel College, served as a senior author. For more than 20 years, he researched TSPO, and his pioneering work in validating the protein as a neuroinflammation biomarker recently earned recognition from the Society of Toxicology.
“This could be potentially a prognostic marker,” Guilarte says. ”If we understand why this change in the structure of the protein produces a worse outcome, then we can potentially come out with therapeutics.” As surgery alone cannot eliminate glioblastoma tumors, discovering new therapies is critical.
Diana Azzam, a Stempel College professor and cancer researcher who devised the study with Guilarte, says that understanding the function of the variant will lead to developing alternative therapies for patients who exhibit it. Azzam specializes in personalized cancer therapeutics and sits on the board of the Society for Functional Precision Medicine.
“There is no question that [the variant] could be playing a role in making the cancer in males more aggressive,” says Azzam, who notes that the variant appears to decrease TSPO’s ability to bind with the body’s natural cholesterol and, consequently, might be impacting steroid production. “The question is, ‘How do we treat this?’ And that’s the next step.”
Guilarte and Azzam launched the study after conferring with Justin D. Lathia, vice chair of cardiovascular and metabolic sciences at Cleveland Clinic Lerner, who calls the results “an exciting new direction and will be the focus of future studies.”
FIU Postdoctoral research associate Arlet M. Acanda de La Rocha and Cleveland Clinic Ph.D. candidate Katie M. Troike completed the laboratory work, and with the help of colleagues at the National Cancer Institute, data was produced in an astonishingly quick six months. The study was funded by the National Institute of Environmental Health Sciences. Funding proposals to continue the work have been submitted.