Gene Expression Profiles of Metabolic Aggressiveness and Tumor Recurrence in Benign Meningioma

Abstract

Around 20% of meningiomas histologically benign may be clinically aggressive and recur. This strongly affects management of meningioma patients. There is a need to evaluate the potential aggressiveness of an individual meningioma. Additional criteria for better classification of meningiomas will improve clinical decisions as well as patient follow up strategy after surgery. The aim of this study was to determine the relationship between gene expression profiles and new metabolic subgroups of benign meningioma with potential clinical relevance. Forty benign and fourteen atypical meningioma tissue samples were included in the study. We obtained metabolic profiles by NMR and recurrence after surgery information for all of them. We measured gene expression by oligonucleotide microarray measurements on 19 of them. To our knowledge, this is the first time that distinct gene expression profiles are reported for benign meningioma molecular subgroups with clinical correlation. Our results show that metabolic aggressiveness in otherwise histological benign meningioma proceeds mostly through alterations in the expression of genes involved in the regulation of transcription, mainly the LMO3 gene. Genes involved in tumor metabolism, like IGF1R, are also differentially expressed in those meningioma subgroups with higher rates of membrane turnover, higher energy demand and increased resistance to apoptosis. These new subgroups of benign meningiomas exhibit different rates of recurrence. This work shows that benign meningioma with metabolic aggressiveness constitute a subgroup of potentially recurrent tumors in which alterations in genes regulating critical features of aggressiveness, like increased angiogenesis or cell invasion, are still no predominant. The determination of these gene expression biosignatures may allow the early detection of clinically aggressive tumors.

Tissue Engineering Strategies as Tools for Personalized Meningioma Treatment

“…Meningiomaderived cells were isolated from meningioma biopsies following Serna et al (9) protocols. Meningiomaderived cells were isolated from meningioma biopsies following Serna et al (9) protocols.…”

“…The NCTC cell (Lonza, Milan, Italy) line was cultured in monolayers in cDMEM. Meningiomaderived cells were isolated from meningioma biopsies following Serna et al (9) protocols. Briefly, fresh tumor samples were disaggregated with 2 mg/mL of collagenase II.…”

Metabolic Alterations in Meningioma Reflect Clinical Course

“…Other authors con rmed these ndings and linked metabolic aggressiveness to distinct genetic and molecular alterations. Serna et al, showed that metabolic aggressiveness was driven by alterations in the expression of IGF1R (Insulin-Growth-Factor1-Receptor), which is involved in the regulation of glycolysis (11). Following the hypothesis of altered glycolysis in meningiomas, it was shown that different parts of the glycolysis are transformed, including PFK (phosphofructokinase) and LDH (lactate dehydrogenase), which were signi cantly increased in anaplastic meningioma compared to other histological subtypes (12).…”

Comparative Proteomic Profiling Using Two-Dimensional Gel Electrophoresis and Identification via LC-MS/MS Reveals Novel Protein Biomarkers to Identify Aggressive Subtypes of WHO Grade I Meningioma

“…4 Despite revisions of the WHO grading criteria over the past two decades, many studies have identified subgroups of benign tumors that do not behave in accordance with grade. [5][6][7][8][9][10][11][12] These tumors rapidly recur after complete resection, or residual tumor beds demonstrate aggressive growth after subtotal resection. Clinically, these "aggressive" Grade I lesions behave in a similar manner to a higher grade lesion, yet remain classified as a Grade I lesion by the WHO grading histological criteria.…”

“…Most of these studies have focused on radiographic characteristics of aggression such as bone invasion which has not been clearly demonstrated to alter recurrence, and even fewer studies focus on recurrent Grade I tumors. 10,11,[14][15][16] Due to the prevalence of aggressive Grade I meningiomas, and an inability to identify these neoplasms, a need exists to identify additional biomarkers to improve diagnostic protocols.…”