Oncotarget

Research Papers:

Functional network analysis of gene-phenotype connectivity associated with temozolomide

Jia Shi, Bo Dong, Peng Zhou, Wei Guan _ and Ya Peng

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Oncotarget. 2017; 8:87554-87567. https://doi.org/10.18632/oncotarget.20848

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Abstract

Jia Shi1,*, Bo Dong1,*, Peng Zhou1,*, Wei Guan1 and Ya Peng1

1Department of Neurosurgery, The Third Affiliated Hospital of Soochow University, Changzhou City, 213003, China

*These authors have contributed equally to this work

Correspondence to:

Wei Guan, email: [email protected]

Ya Peng, email: [email protected]

Keywords: temozolomide, glioma, TP53

Received: June 26, 2017    Accepted: August 17, 2017    Published: September 12, 2017

ABSTRACT

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.


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