Intratumoral heterogeneity of meningioma with respect of the methylation profiling

Abstract

Introduction. Despite a relatively favorable prognosis of meningiomas, this nosological group remains a serious diagnostic challenge, largely due to the shortage of accurate diagnostic methods. Identification of methylation classes (MC) of meningiomas is becoming increasingly popular, since it can improve the prognostic accuracy. The aim of this study was to compare most promising methods for tissue molecular analysis. Methods. This article focuses on comparing two promising diagnostic approaches, namely, global genome methylation profiling and identification of cluster types (CT) of meningioma cells based on their potential diagnostic significance. Also, basic correlation factors of these two methods were assessed. The identification of CT is based on characterizing cell functional features by the marker molecular factors that indicate the activation of proliferative and metabolic processes. Technically, our approach included obtaining full-format scans of immunohistochemical slides, their stepwise median filtration, and specific masking regimes followed by creation of complex multilayer images with maximally precise coordinate correlation. All data on the expression activity of the molecular factors were used for a cluster analysis to identify tumor cell clusters for their subsequent secondary clusterization into 8 CTs. Results. The study showed unidirectional progression of the tumor malignancy and biological aggressiveness based on identification of the MC composition or the TC content. At the same time, for meningiomas, the TC approach was superior to the MC approach by its prognostic value. A combination of these methods provided the most effective prognosis. Conclusion. The meningioma cell functional profiling with cluster identification is very promising as it can expand the diagnostic frontier. Further development of such comprehensive approaches that include other molecular methods will provide critically new quality of the diagnostic process.