Meningiomas are the most common primary intracranial tumors. Current treatment relies on surgical resection and radiotherapy, but molecular predictors for recurrence are lacking. This study aims to investigate epigenetic features, specifically histone post-translational modifications (PTMs) and DNA methylation, to stratify patients. The study involves a retrospective cohort to define an epigenetic signature and a prospective cohort to validate it in tissues and liquid biopsies (plasma/EVs).

The study is shaped by two phases. The first is a histone PTMs analysis in solid tissues from a retrospective cohort of 150 meningioma FFPE samples. The second step consists of validating the epigenetic signature in a prospective cohort of patients (n=60). The study addresses four main objectives: 1) Dissecting the informative power of epigenetic signatures (histone PTMs by MS) in tissues; 2) Validating signatures in prospective tissues and matched sera (circulating nucleosomes); 3) Assessing DNA methylation profiles from plasma-derived Extracellular Vesicles (EVs); 4) Developing a Machine Learning model integrating epi-proteomics, DNA-methylation, and clinical data for prognostic subtyping.

Inclusion Criteria:

Inclusion Criteria (Retrospective & Prospective):

• Patient aged 18 years or older.
• First diagnosis of uni-focal meningioma of the convexity.
• Macroscopical total resection (Simpson 1-3).

(Retrospective only):

• Surgery performed between 2007 and 2016;
• availability of FFPE sample and medical records.

Exclusion Criteria:

• Genetic syndromes.
• Diffuse Meningeal Meningiomatosis.
• Patients who underwent experimental treatment in neo-adjuvant setting.

(Prospective only):

• Previous surgical/medical treatment for another meningioma;
• positive oncological history (e.g., breast cancer).

Patients with Meningioma