Functional network analysis of gene-phenotype connectivity associated with temozolomide

Rationale: Glioma has a poor survival rate in patients even with aggressive treatment. Temozolomide (TMZ) is the standard chemotherapeutic choice for treating glioma, but TMZ treatment consistently leads to high resistance. Aim: To investigate the underlying mechanisms of TMZ action with new therapeutic regimens in glioma. Methods and results: The biological effects of TMZ mainly depend on the three following DNA repair systems: methylguanine methyltransferase (MGMT), mismatch repair (MMR) and base excision repair (BER). Based on related genes in these three systems, web-based tools containing data compiled from open-source databases, including DrugBank, STRING, WebGestalt and ClueGO, were queried, and five common genes along with the top fifteen pathways, including the glioma pathway, were identified. A genomic analysis of the six genes identified in the glioma pathway by cBioPortal indicated that TMZ might exert biological effects via interaction with the tumor protein P53(TP53) signaling axis. Finally, a survival analysis with the six genes in glioma cases (low-grade glioma and glioblastoma multiforme) was conducted using OncoLnc, which might provide directions for the future exploration of prognosis in glioma. Conclusions: This study indicates that a functional network analysis resembles a BioGPS, with the ability to draw a web-based scientific map that can productively and cost-effectively associate TMZ with its primary and secondary biological targets.