Integrated proteomic and metabolomic profiling the global response of rat glioma model to temozolomide treatment

ABSTRACT: Temozolomide (TMZ) is the first-line chemotherapeutic drug for glioblastoma treatment. It can induce O6-methylguanine DNA lesions, lead to prolonged G2–M arrest and ultimately cell death. However, the molecular response involved in TMZ inhibiting tumor growth has not been fully elucidated. In this study, by integrating tandem mass tag (TMT)-based quantitative proteomics and metabolomics, we aimed to discover the protein-metabolite regulatory network in a rat allograft glioma model and to identify protein and metabolite markers that correlate with TMZ treatment. A total of 1,782 proteins and 56 endogenous metabolites were significantly altered in the brain between sham and tumor groups, 38 metabolites markedly altered in plasma. After TMZ treatment, 251 proteins and 9 metabolites significantly changed in the brain tended to return to normal levels, and 14 metabolites did in plasma. 6 metabolites in brain tissue were predicted to be potential biomarkers for TMZ treatment. Integrative multi-omics analysis revealed significant changes in proteins and metabolites involved in DNA replication, nucleotides degradation, cysteine biosynthesis, and synaptogenesis signaling pathway. Adenosine, sarcosine and adenosine deaminase involved in multiple metabolic pathways may serve as potential biomarkers for TMZ treatment. This is the first report which integrating multi-omics data to investigate the global response of proteins and metabolites in rat glioma under TMZ treatment, and it can provide a comprehensive insight to screen potential targets and biomarkers of glioma as well as to elucidate the mechanism of TMZ.

ORGANISM(S): Rattus Norvegicus

SUBMITTER: Jinlan Zhang  

PROVIDER: PXD013790 | iProX | Thu May 09 00:00:00 BST 2019

REPOSITORIES: iProX