Glial fibrillary acidic protein, neurofilament light, matrix metalloprotease 3 and fatty acid binding protein 4 as non-invasive brain tumor biomarkers

Abstract

Background: Gliomas are aggressive malignant tumors, with poor prognosis. There is an unmet need for the discovery of new, non-invasive biomarkers for differential diagnosis, prognosis, and management of brain tumors. Our objective is to validate four plasma biomarkers – glial fibrillary acidic protein (GFAP), neurofilament light (NEFL), matrix metalloprotease 3 (MMP3) and fatty acid binding protein 4 (FABP4) – and compare them with established brain tumor molecular markers and survival. Methods: Our cohort consisted of patients with benign and malignant brain tumors (GBM= 77, Astrocytomas= 26, Oligodendrogliomas= 23, Secondary tumors= 35, Meningiomas= 70, Schwannomas= 15, Pituitary adenomas= 15, Normal individuals= 30). For measurements, we used ultrasensitive electrochemiluminescence multiplexed immunoassays. Results: High plasma GFAP concentration was associated with GBM, low GFAP and high FABP4 were associated with meningiomas, and low GFAP and low FABP4 were associated with astrocytomas and oligodendrogliomas. Several prognostic genetic alterations were significantly associated with plasma biomarker levels. We found no independent associations between plasma GFAP, NEFL, FABP4 and MMP3, and overall survival. The candidate biomarkers could not reliably discriminate GBM from primary or secondary CNS lymphomas. Conclusions: GFAP, NEFL, FABP4 and MMP3 are useful for differential diagnosis and prognosis, and are associated with molecular changes in gliomas.