Background and Significance: Meningioma and glioma are the most prevalent primary brain tumor. Gliomas are commonly malignant and invade the normal brain tissues, whereas meningiomas are mostly indolent and benign in nature. However, higher grades of meningioma have a high recurrence risk and invasive potential. Owing to the proximity of the cerebrospinal fluid (CSF) with the central nervous system, and the presence of blood-brain barrier, makes CSF a reservoir of diagnostic and prognostic markers. In this light, an inter-grade comprehensive proteomic analysis of gliomas and meningiomas has been designed to understand the altered physiology of these tumors.
Experimental design: Differential CSF proteome profiling of meningioma grade I (n=5), meningioma grade II (n=4), LGG (n=3), GBM (n=4) and control (n=5) samples was performed by using label-based quantitative approach. The significantly altered proteins were subjected to gene ontology analysis to map their functional and biological role and a few were validated using targeted proteomic approach.
Results: Proteins associated with modulation of immune response, lipid metabolism, remodeling of extra-cellular matrix, cell surface interactors and platelet activation were found to be significantly altered. Level of several proteins including gelsolin, ENPP2, SEMA7A, CD14, osteopontin, showed significant de-regulation in the CSF of both the malignancies, and can be a putative indicator of neoplasm formation. Intriguingly, proteome trends of meningioma grade I samples was strikingly different from that of glioma and meningioma grade II samples, suggesting the differential proteome composition of benign tumors.
Conclusions: This pilot study was designed to understand the physiological modulation in the CSF of two prevalent brain malignancies to understand the underlying mechanism of tumor growth and progression. The study revealed a few candidate tumor-specific markers that can be indicative of the neoplastic growth in the CNS, which on further validation can aid in supplementing the current diagnostic and prognostic modalities.