The chemical exposome in brain cancer: an exploratory study.

Diffuse gliomas are a highly heterogeneous and aggressive brain tumours with poor prognosis and survival and few established risk factors. Environmental exposures are suspected in the pathogenesis of these tumours; however, results of existing studies are limited and inconsistent, particularly for exogenous organic chemicals, with no available characterization of the chemical exposome of these tumours. Also, better understanding of phenotypic differences in tumour types is needed in order to improve clinical decision making and provision of personalised treatment recommendations. In this proof-of-concept study we analysed 33 glioblastoma samples (Bellvitge Glioma Cohort (BGC), Spain, 2005-present), including 16 methylated and 17 non-methylated tumours combining HRMS-based wide-scope target and suspect strategies. Forty-six exogenous chemicals were identified in the tumour tissue samples (31 confirmed with standard) including a variety of industrial chemicals (e.g. plastic additives or perfluorinated compounds), personal care products and pharmaceuticals. Our findings provide novel evidence on the presence of these chemicals in brain tissue, highlighting the need for comprehensive evaluations of their potential effects in the tumour pathogenesis. Finally, after applying metabolomics methods we observed clear differences in the profiles of endogenous chemicals among the studied glioma subtypes, and identified possible biomarkers. These chemicals have potential to be determined in a non-invasive manner, either by LCHRMS-based blood analysis or using complementary techniques (proton magnetic resonance (1H-MRS)). These are inspiring results since methylation is a strong independent predictor of survival as well as tumour response to chemotherapy for glioblastoma. Indeed, its non-invasive and pre-surgical determination would have a major impact on patient management. Our preliminary data is suggestive for the potential of nontargeted exposome methods to find new valuable biomarkers for diffuse gliomas diagnostic and prognostic stratification.