Abstract

BackgroundLung cancer has been a common malignant tumor with a leading cause of morbidity and mortality, current molecular targets are woefully lacking comparing to the highly progressive cancer. The study is designed to identify new prognostic predictors and potential gene targets based on bioinformatic analysis of Gene Expression Omnibus (GEO) database.MethodsFour cDNA expression profiles GSE19188, GSE101929, GSE18842 and GSE33532 were chosen from GEO database to analyze the differently expressed genes (DEGs) between non-small cell lung cancer (NSCLC) and normal lung tissues. After the DEGs functions were analyzed, the protein–protein interaction network (PPI) of DEGs were constructed, and the core gene in the network which has high connectivity degree with other genes was identified. We analyzed the association of the gene with the development of NSCLC as well as its prognosis. Lastly we explored the conceivable signaling mechanism of the gene regulation during the development of NSCLC.ResultsA total of 92 up regulated and 214 down regulated DEGs were shared in four cDNA expression profiles. Based on their PPI network, TOP2A was connected with most of other genes and was selected for further analysis. Kaplan–Meier overall survival analysis (OS) revealed that TOP2A was associated with worse NSCLC patients survival. And both GEPIA analysis and immunohistochemistry experiment (IHC) confirmed that TOP2A was aberrant gain of expression in cancer comparing to normal tissues. The clinical significance of TOP2A and probable signaling pathways it involved in were further explored, and a positive correlation between TOP2A and TPX2 expression was found in lung cancer tissues.ConclusionUsing bioinformatic analysis, we revealed that TOP2A could be adopted as a prognostic indicator of NSCLC and it potentially regulate cancer development through co-work with TPX2. However, more detailed experiments are needed to clarify its drug target role in clinical medical use.

Highlights

  • Lung cancer has been a common malignant tumor with a leading cause of morbidity and mortality, current molecular targets are woefully lacking comparing to the highly progressive cancer

  • Identification of 306 differently expressed genes (DEGs) shared by four Gene Expression Omnibus (GEO) profiles We chose four cDNA expression profiles GSE18842, GSE19188, GSE33532 and GSE101929 from GEO database to analyze the DEGs between non-small cell lung cancer (NSCLC) and normal lung tissues

  • The results of gene ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) revealed that the cellular components of 214 down-regulated DEGs were mainly enriched in plasma membrane and extracellular space, the biological processes were focused on cell communication and signal transduction, and the signaling pathways were mostly epithelial to mesenchymal transition related (Fig. 2b)

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Summary

Introduction

Lung cancer has been a common malignant tumor with a leading cause of morbidity and mortality, current molecular targets are woefully lacking comparing to the highly progressive cancer. NSCLC includes lung adenocarcinoma, squamous cell carcinoma and large cell carcinoma. Not to mention the other subtypes of NSCLC besides adenocarcinoma, including squamous carcinoma and large cell carcinoma, the drug targets are woefully numbered currently. TOP2A, which is short for Topoisomerase II Alpha, locates at 17q21.2 and encodes an enzyme that controls and alters the topological states of DNA during transcription This enzyme has been known to be involved in processes such as chromosome condensation, chromatid separation, and the relief of torsional stress that occurs during DNA transcription and replication. Pabla et al [48] reported that TOP2A could be a potential new indicator

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