Differential Expression of Proteins and Genes at the Tumor-Brain Interface in Invasive Meningioma

Most meningiomas are dural-based extra-axial tumors in close contact with the brain. Expression of genes and proteins at the tumor-brain interface in brain-invasive meningioma is basically unknown. Using the NanoString pan-cancer panel, differential expression of genes in the invasive edge versus main tumor body was determined in 12 invasive meningiomas (comprising the discovery cohort), and 6 candidate genes: DTX1, RASGRF1, GRIN1, TNR, IL6, and NR4A1, were identified. By immunohistochemistry, DTX1 and RASGRF1 expression correlated with gene expression, and were studied in an expanded cohort of 21 invasive and 15 noninvasive meningiomas, together with Ki-67. Significantly higher expression of DTX1, RASGFR1, and Ki-67 was found in the invasive edge compared with the main tumor body. Increased expression of RASGRF1 and Ki-67 was more clearly associated with brain invasion. The situation with DTX1 was less definitive since increased expression was observed in meningiomas both at the invasive edge and when in close contact with brain but without invasion. Pathway analyses identified significant links between DTX1 and RASGRF1 and key biological processes, including cell-cell adhesion, and signaling pathways including Notch, RAS, MAPK, and Rho. Higher expression of DTX1, RASGRF1, and Ki-67 in the brain-invasive area of meningiomas suggests that these proteins play a role in the process of brain invasion.