1045 Detection of P53 Aggregates for Plasma-Based Diagnosis and Monitoring of Glioblastoma

Abstract:

INTRODUCTION: Although ordinarily a pivotal tumour-suppressor, p53 can form amyloid aggregates that lose tumour-suppressing functions and exert tumour-promoting activities. Detection of p53 aggregates in liquid biopsies may be a more cost-effective alternative for diagnosis, monitoring and prognostication of glioblastoma (GB) that avoids the logistical challenges of MRI. We have previously developed a novel ultrasensitive immunoassay based on the single-molecule array technology (SiMoA) for detecting p53 aggregates in plasma. METHODS: Plasma samples were collected intraoperatively from newly diagnosed GB patients during the initial surgery, and from matched control patients undergoing non-cancer surgery. Follow-up samples were collected during outpatient clinics. The assay was used to measure and compare plasma p53 aggregate levels between pre-surgery GB patients and controls. To evaluate the correlation between p53 levels and longitudinal outcome, we identified patients for whom plasma samples were available at =2 timepoints and retrospectively reviewed their health records to map p53 concentrations to onset of treatment (surgery, radiotherapy and/or chemotherapy), survival and tumour recurrence (as indicated by MRI). RESULTS: The assay demonstrated a diagnostic accuracy of 91.48% in distinguishing between GB patients (n=185) and controls (n=35). In our longitudinal review, all patients (n=25) demonstrated clinical congruence with p53 levels either through a rise in p53 levels prior to tumour recurrence (40%), a decline in p53 levels post-treatment (16%), or a combination of these two patterns (44%). Kaplan-Meier curves showed no statistically significant association between p53 levels and survival. CONCLUSIONS: Our study highlights the potential utility of plasma p53 aggregate levels for early detection, diagnosis and monitoring of patients with brain cancer. Earlier detection of both primary and recurrent disease in GB would enable rapid institution of treatment thereby maximising the potential for patient benefit.

Authors:

JYL Lam, R Chintapalli, D Boeken, Z Zhang, E Fertan, Z Xia, JSH Danial, RT Ranasinghe, G Tsang-Pells, L Julian, KM Brindle, R Mair, D Klenerman

Journal:

Neurosurgery

Citation info:

71(Supplement_1):144-144

Publication date:

1st Apr 2025

Full text

DOI