Neuroinflammation protein linked to worse survival in men with
glioblastoma

Date:
October 18, 2021
Source:
Florida International University
Summary:
Scientists have discovered a new link that could bring the
scientific and medical community closer to understanding why
glioblastoma, the most common malignant brain tumor, is deadlier
in males than females.



FULL STORY ========================================================================== Scientists have discovered a new link that could bring the scientific
and medical community closer to understanding why glioblastoma, the most
common malignant brain tumor, is deadlier in males than females.


==========================================================================
A new study by Florida International University's Robert Stempel College
of Public Health & Social Work, Cleveland Clinic Lerner Research Institute
and the National Cancer Institute, part of the National Institutes of
Health, reveals, for the first time, a connection between translocator
protein 18 kDa (TSPO), a widely used biomarker of neuroinflammation,
and survival outcomes in glioblastoma patients. Findings suggest
that a variation in the protein's structure correlates with worse
survival outcomes in males than females. The study was published in the September special issue "Infiltrative Gliomas: Emerging Insights into Pathophysiology, Diagnosis, and Management" of the Cancers journal.

"This is a fascinating observation because glioblastoma has sex-specific differences," said Diana Azzam, assistant professor at Stempel College,
who was corresponding author of the study. "It's more frequent in males
than females, and the survival outcome of males is worse than females. In
the future, this can potentially help patients receive personalized
treatments for the disease." Azzam worked closely with the study's lead authors Katie M. Troike, Ph.D.

candidate in the Molecular Medicine Ph.D. program at Cleveland Clinic, and Arlet M. Acanda de la Rocha, a postdoctoral associate at Stempel College.

"I've studied TSPO for more than 20 years and knew that it was highly
expressed in glioblastomas. This outstanding research team is beginning to uncover its role in one of the deadliest cancers," said Toma's Guilarte, scientist, professor and dean of Stempel College, who was a senior author
of the study.

"We hope this research will lead to finding better treatments and,
one day, a cure." Glioblastoma is found in adults and is 1.6 times
more likely to affect males than females. Each year, approximately
12,000 people in the U.S. are diagnosed with glioblastoma. Patients
diagnosed with glioblastoma experience symptoms like seizures, persistent headaches, or loss of brain function like memory loss and personality
changes. Glioblastomas have devastating consequences for patients. The
median survival time is 12 to 14 months, and less than 7% of patients
survive more than five years. Thus, better treatments and strategies
for improving prognosis are urgently needed as there is no cure for
the disease.

Researchers analyzed the blood samples of 441 glioblastoma male and female patients to evaluate the correlation between the TSPO polymorphic variant rs6971, one of the most frequent polymorphisms (variants) found in humans,
with the clinical outcomes of glioblastoma patients. Compared with female glioblastoma patients, males with the TSPO variant had shorter overall
and progression-free survival times. There was no association between
the variant and survival time in females. The study suggests that, as
a predictor of poor prognosis, the variant has potential for use as a prognostic biomarker in glioblastoma patients.

"We have been thinking about sex differences in glioblastoma in terms
of immune responses and this collaborative study provides an unexpected
example of a polymorphism that shows a sex difference, suggesting that
there are likely others that function in a similar manner," said Justin
D. Lathia, vice chair of the Department of Cardiovascular & Metabolic
Sciences at Cleveland Clinic's Lerner Research Institute and one of the
study's senior authors. "This is an exciting new direction and will be
the focus of future studies." The research team also included colleagues
from the National Cancer Institute led by Jill Barnholtz-Sloan, associate director, informatics and data science, in the Center for Biomedical Informatics and Information Technology and senior investigator in the
Division of Cancer Epidemiology and Genetics.

Azzam said this will be the first of many studies related to the use of
TSPO as a prognostic biomarker.

"What we really need to do is understand the function of this
polymorphism. Why is it associated with worse survival in male
patients? Why do we see biological sex-specific differences? We have so
many questions now," she said.

The study was funded by the National Institute of Environmental Health
Sciences and FIU's Office of Research & Economic Development.

========================================================================== Story Source: Materials provided by
Florida_International_University. Original written by Stephanie
Rendon. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Katie M. Troike, Arlet M. Acanda de la Rocha, Tyler J. Alban,
Matthew M.

Grabowski, Balint Otvos, Gino Cioffi, Kristin A. Waite, Jill
S. Barnholtz Sloan, Justin D. Lathia, Toma's R. Guilarte, Diana
J. Azzam. The Translocator Protein (TSPO) Genetic Polymorphism
A147T Is Associated with Worse Survival in Male Glioblastoma
Patients. Cancers, 2021; 13 (18): 4525 DOI: 10.3390/cancers13184525 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/10/211018150655.htm

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