Serum protein biomarkers linked to neurodegenerative processes are elevated in glioma patients and associated with severity of neurologic symptoms

Authors

• E Hsieh
• T Mendoza
• D Raval
• MC Kauss
• K Slattery
• M Wright
• T Davis
• A Choi
• K Reinhart
• H Miller
• E Vera
• TS Armstrong
• VA Guedes

Abstract

Background: Glioma patients frequently report neurologic symptoms, adding to the complexity of cancer management and negatively impacting patient's quality of life. Despite its clinical relevance, mechanisms associated with the development of neurologic symptoms in glioma patients remain unclear. We tested the hypothesis that the circulating levels of proteins previously linked to central nervous system (CNS) damage and neurodegeneration are elevated in glioma patients and associated with neurologic symptom severity. Methods: Patients (n=73) were enrolled in a natural history study. Healthy subjects (n=39) were recruited by the National Institutes of Health Clinical Center Blood Bank. Neurologic symptom severity and walking interference were assessed using MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT). Serum proteins were analyzed using ultrasensitive assays (Meso Scale Discovery). Results: Participants were predominantly white and male with a median age of 44 for patients and 49 for healthy volunteers. No significant differences in age, sex, or race were observed between patients and healthy subjects. Serum levels of NfL (p<0.0001), GFAP (p<0.0001), and tau (p<0.0001) were higher in glioma patients when compared to healthy subjects. Patients with walking interference had higher levels of GFAP (p=0.003), NfL (p=0.003), and tau (p=0.004), and those who reported numbness had higher levels of GFAP (p=0.012). Conclusions: Serum levels of protein markers of neurodegeneration are elevated in glioma patients and associated with the presence of neurologic symptoms. Blood-based biomarkers have the potential to shed light on the mechanisms underlying symptoms and offer a non-invasive alternative for monitoring CNS damage and patient outcomes.

Scientific Focus Area: Clinical Research

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