CIRCULATING PROGNOSTIC BIOMARKERS IN MENINGIOMA: S100A4 AND FIBULIN-2

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Abstract AIMS We aim to identify circulating prognostic biomarkers that accurately identify high risk meningioma whilst reducing the burden of invasive diagnostics. In our proteomic analysis, S100A4 and Fibulin-2 are significantly over expressed in grade 2 tumours compared to grade 1. They are both calcium-binding proteins with S100A4 involved in mesenchymal transition while Fibulin-2 helps scaffold the extracellular matrix. Elevated levels correlate with aggressive phenotypes in multiple cancers. METHOD Anonymised pre-operative meningioma blood samples were obtained from ‘The Plymouth Brain Tumour Biobank’ and ‘UK Brain Archive Information Network (BRAIN-UK)’. In total, 155 samples were analysed via Enzyme-Linked Immunosorbent Assay (ELISA) for serum S100A4 and plasma Fibulin-2. The Area Under the Receiver Operating Characteristic (ROC) curve (AUC) was used to examine the specificity and sensitivity of both markers. RESULTS Circulating levels of S100A4 were significantly (*p<0.05) higher in grade 2 meningiomas (mean 276.7 pg/mL (+/- 49.9 pg/mL) compared to grade 1 (mean 153.10 pg/mL +/- 20.68 pg/mL). Serum S100A4 & plasma Fibulin-2 cut-off values of 344.8 pg/mL & 2500 pg/mL respectively have a 95% specificity for identifying patients with grade 2 tumours over grade 1. To improve the diagnostic accuracy of grade 1 vs grade 2 samples, we combined S100A4 and Fibulin-2 concentrations to achieve an improved AUC of 0.682, *p<0.05. CONCLUSIONS Serum S100A4 is significantly higher in grade 2 compared to grade 1 meningiomas (95% sensitivity; cut off 344.8 pg/mL). Combining S100A4 and the previously published Fibulin-2 improves the accuracy of predicting grade 2 meningiomas.

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