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Anticancer Agents Med Chem. 2019 Jul 12. doi: 10.2174/1871520619666190712203217. [Epub ahead of print]

The Pharmacogenomics "Side-Effect" of TP53/EGFR in Non-Small Cell Lung Cancer Companied with Atorvastatin Therapy: A Functional Network Analysis.

Author information

1
Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Wuhan,. China.
2
Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan,. China.

Abstract

BACKGROUND:

Atorvastatin belongs to the group of statins, which is leading drugs for hypercholesterolemia treatment. Meanwhile, its anticancer effect is emerged and highly appreciated, but the properties are still unclear. The aim of this study was to explore the underlying anticancer mechanisms induced by atorvastatin and enlarge the potential target in non-small cell lung cancer.

METHODS:

Target genes of atorvastatin were collected in the DrugBank database. Prediction of interaction between primary targets and secondary targets was performed, and protein-protein interaction network was constructed though the STRING. Then, KEGG pathway enrichment analysis was performed with WebGestalt and ClueGO, which including the pathways in non-small cell lung cancer. Furthermore, a genomic alteration analysis of the selected seed genes of atorvastatin benefit and in non-small cell lung cancer pathway was made by cBioPortal. Finally, a survival analysis with the selected seed genes in lung cancer (lung adenocarcinoma, lung squamous cell carcinoma) was conducted using Kaplan-Meier (KM) plotter.

RESULTS:

Totally, to identify seed genes, 65 potential candidate genes were screened as targets for atorvastatin using STRING with DrugBank database, while the KEGG pathway was enriched to get the overlap match of pathways in non-small cell lung cancer. Then 4 seed genes, Epidermal Growth Factor Receptor (EGFR), erb-b2 receptor tyrosine kinase 2 (ERBB2), AKT serine/threonine kinase 1 (AKT1) and tumor protein p53 (TP53), were selected and their genomic alternation were evaluated in cBioPortal. Survival analysis found that TP53 and EGFR showed a significant correlation (log rank P = 3e-07 and 0.023) with lung adenocarcinoma and lung squamous cell carcinoma, according to KM analysis.

CONCLUSION:

Gene-phenotype connectivity for atorvastatin in non-small cell lung cancer was identified using functional/activity network analysis method, and our findings demonstrated that TP53 and EGFR could be the potential targets in cancer patients with atorvastatin therapy.

KEYWORDS:

AKT1 ; Atorvastatin; EGFR; TP53; functional/activity network analysis; non-small cell lung cancer

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