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Prognostic significance of TOP2A in non-small cell lung cancer revealed by bioinformatic analysis.

ABSTRACT: Background: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. The study is designed to identify new prognostic predictors and potential gene targets based on bioinformatic analysis of Gene Expression Omnibus (GEO) database. Methods:Four 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. Results:A 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. Conclusion:Using 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.

SUBMITTER: Ma W

PROVIDER: S-EPMC6737627 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Prognostic significance of TOP2A in non-small cell lung cancer revealed by bioinformatic analysis.

Ma Wenxia W Wang Bin B Zhang Yaping Y Wang Ziyue Z Niu Dan D Chen Siyu S Zhang Zhirong Z Shen Ningning N Han Weixia W Zhang Xiaoqin X Wei Rong R Wang Chen C

Cancer cell international 20190911

<h4>Background</h4>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. The study is designed to identify new prognostic predictors and potential gene targets based on bioinformatic analysis of Gene Expression Omnibus (GEO) database.<h4>Methods</h4>Four cDNA expression profiles GSE19188, GSE101929, GSE18842 and GSE33532 were chosen from GEO database to analyze the ...[more]

PMID: 31528121

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Project description:The majority of lung cancers belong to the non-small-cell lung cancer (NSCLC) category, which is linked to a high mortality rate despite significant progress in diagnosis and treatment. Therefore, there is a need for novel prognostic NSCLC biomarkers to improve prognosis which currently remains poor. Recent studies and analyses of gene expression data of NSCLC revealed that high expression of KIAA1522 was significantly associated with poor prognosis and decreased overall survival. We identified 98 patients who underwent radical curative surgical resections or metastasectomy for pulmonary adenocarcinoma and squamous cell carcinoma at our institution or the pathological diagnosis confirmed by our pathologists. Following the latest data, we utilized immunohistochemistry to assess the expression of KIAA1522 and investigated its association with various clinic-demographic parameters, pathological stages, recurrence rates, overall survival, and disease-free survival in patients who achieved complete remission. Notably, there were no significant differences in the expression profiles of KIAA1522 between adenocarcinoma and squamous cell carcinoma samples (p=0.6). Survival analysis was conducted using log-rank tests and a multivariate Cox proportional hazard model. Of the 98 samples, 54 (55.1%) exhibited high expression of KIAA1522, and patients with high KIAA1522 expression had a significantly shorter overall survival than the low-expression group (p=0.01). Multivariate Cox proportional hazard models in which metastatic patients were included revealed that along with older age, higher TNM stage (tumor, node, metastasis system), and Eastern Cooperative Oncology Group (ECOG) performance status, high expression of KIAA1522 served as an independent prognostic factor. A high expression profile was not significantly associated with relapses in those whose complete remission had been achieved. Still, those patients with high expression of KIAA1522 tended to exhibit a shorter disease-free survival rate. In conclusion, our findings suggest that KIAA1522 expression is an independent factor for predicting overall survival and may serve as a valuable prognostic indicator for relapse and disease-free survival in NSCLC patients.

Dataset Information

Prognostic significance of TOP2A in non-small cell lung cancer revealed by bioinformatic analysis.

Publications

Prognostic significance of TOP2A in non-small cell lung cancer revealed by bioinformatic analysis.

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