Impact of a cell cycle and an extracellular matrix remodeling transcriptional signature on tumor progression and correlation with EZH2 expression in meningioma.

Autor:	Pereira BJA; 1Department of Neurology, Laboratory of Molecular and Cellular Biology, University of São Paulo, São Paulo, Brazil., Marcondes Lerario A; 2Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Ann Arbor, Michigan., Sola PR; 1Department of Neurology, Laboratory of Molecular and Cellular Biology, University of São Paulo, São Paulo, Brazil., Laurentino TS; 1Department of Neurology, Laboratory of Molecular and Cellular Biology, University of São Paulo, São Paulo, Brazil., Mohan DR; 3Medical Scientist Training Program, and Doctoral Program in Cancer Biology, University of Michigan, Ann Arbor, Michigan., de Almeida AN; 4Neurosurgery Division, Department of Neurology, University of São Paulo, São Paulo, Brazil., Pires de Aguiar PH; 5Medical Research ABC Medical School, Santo André, Brazil.; 6Pontifice Catholic University of São Paulo, Sorocaba, Brazil; and., da Silva Paiva W; 4Neurosurgery Division, Department of Neurology, University of São Paulo, São Paulo, Brazil., Wakamatsu A; 7Department of Pathology, Hepatic Pathology Laboratory, University of São Paulo, São Paulo, Brazil., Teixeira MJ; 4Neurosurgery Division, Department of Neurology, University of São Paulo, São Paulo, Brazil., Oba-Shinjo SM; 1Department of Neurology, Laboratory of Molecular and Cellular Biology, University of São Paulo, São Paulo, Brazil., Marie SKN; 1Department of Neurology, Laboratory of Molecular and Cellular Biology, University of São Paulo, São Paulo, Brazil.
Jazyk:	angličtina
Zdroj:	Journal of neurosurgery [J Neurosurg] 2022 Aug 26; Vol. 138 (3), pp. 649-662. Date of Electronic Publication: 2022 Aug 26 (Print Publication: 2023).
DOI:	10.3171/2022.7.JNS22953
Abstrakt:	Objective: The authors searched for genetic and transcriptional signatures associated with tumor progression and recurrence in their cohort of patients with meningiomas, combining the analysis of targeted exome, NF2-LOH, transcriptome, and protein expressions. Methods: The authors included 91 patients who underwent resection of intracranial meningioma at their institution between June 2000 and November 2007. The search of somatic mutations was performed by Next Generation Sequencing through a customized panel and multiplex ligation-dependent probe amplification for NF2 loss of heterozygosity. The transcriptomic profile was analyzed by QuantSeq 3' mRNA-Seq. The differentially expressed genes of interest were validated at the protein level analysis by immunohistochemistry. Results: The transcriptomic analysis identified an upregulated set of genes related to metabolism and cell cycle and downregulated genes related to immune response and extracellular matrix remodeling in grade 2 (atypical) meningiomas, with a significant difference in recurrent compared with nonrecurrent cases. EZH2 nuclear positivity associated with grade 2, particularly with recurrent tumors and EZH2 gene expression level, correlated positively with the expression of genes related to cell cycle and negatively to genes related to immune response and regulation of cell motility. Conclusions: The authors identified modules of dysregulated genes in grade 2 meningiomas related to the activation of oxidative metabolism, cell division, cell motility due to extracellular remodeling, and immune evasion that were predictive of survival and exhibited significant correlations with EZH2 expression.
Databáze:	MEDLINE
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