374 Cell Cycle as a Biological Marker of Aggressiveness and Therapeutic Target in Meningiomas

Abstract

INTRODUCTION: Meningiomas are the most common intracranial tumors, accounting for 36% of cases. The World Health Organization (WHO) classifies these tumors into three histological grades: benign (grade I), atypical (grade II) and anaplastic (grade III). Although most lesions are benign, the treatment that is currently widely recommended is restricted to surgery and/or radiotherapy, which are often insufficient for aggressive lesions or lesions that involve neurovascular structures, making the treatment of meningiomas a challenge even today. The understanding of molecular changes in meningiomas may contribute to the identification of aggressiveness markers and possible new therapeutic targets. METHODS: The expressions of approximately 800 genes were evaluated, using the PanCancer Nanostring Kit, in 17 meningiomas (6 benign, 6 atypical and 5 anaplastic) and 6 control arachnoids. Comparisons of gene expression between samples of different histological grades and between tumor and control arachnoid samples were performed and the results tabulated in heatmaps after analysis by bioinformatics tools (NSolver, R Statistics, and DAVID, ROSALIND and COSMIC online databases). RESULTS: The molecular cell cycle pathway has components upregulated in the three grades of meningiomas analyzed and significantly induced in histologically more aggressive meningiomas. Hyper-regulated genes may be candidates for markers of aggression. In addition, cell cycle induction can be a therapeutic target in more aggressive meningiomas, with the introduction of cell cycle blocking drugs. CONCLUSIONS: The hyper-regulated cell cycle pathway may be associated with aggressiveness in meningiomas. Cell cycle induction in meningiomas can be a therapeutic target for the treatment of these tumors, through cell cycle blockers. Additional studies are needed to corroborate the findings of this study.