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Published on: March 30, 2019
Upregulated cyclins may be novel genes for triple-negative breast cancer based on bioinformatic analysis
Yongbin Lu1,2, Gang Yang3, Yi Xiao4
1Scientific Development and Planning Department, The First Hospital of Lanzhou University, Lanzhou, China.
Background:
Triple-negative breast cancer (TNBC) is one of the leading causes of death among females around the world. However, the molecular mechanism of the disease among TNBC patients remains to be further studied.
Methods:
In our study, four microarray data and two high throughput sequencing data were acquired from the GEO database, and the differentially expressed genes (DEGs) between TNBC and normal tissues had been analyzed. Analysis of functional enrichment and pathway enrichment of DEGs was conducted by the Funrich software, and protein-protein interaction (PPI) network gained from the STRING, and hub genes were confirmed by the Cytoscape. Kaplan-Meier plotter (KM plotter) online dataset had been used to analyze DEGs of overall survival (OS), and progression-free survival (PFS).
Results:
In total, 1638 DEGs were gained in our study covering 984 upregulated and 654 downregulated genes. Moreover, a PPI network was constructed, and cyclin-dependent kinase 1 (CDK1), cyclin B1 (CCNB1), and cyclin A2 (CCNA2) were found as top genes with higher node degrees. CDK1, CCNA2, and CCNB1were obviously enriched in the cell cycle. The top upregulated genes including CDK1, CCNB1, CCNA2, and PLK1 were overexpressed in TNBC, and correlated with worse OS in breast cancer. High expression of CCNB1 was correlated with worse PFS in TNBC (HR = 1.42, 95% CI: 1.04-1.94, P = 0.028). Besides, there was a correlation between CCNB1 and CDK1 in TNBC, as well as between CCNA2 and CDK1 (r = 0.804, P < 0.001; r = 0.577, P < 0.001, respectively).
Conclusion:
Our results suggest that cyclin CDK1, CCNB1, and CCNA2 are overexpressed in TNBC and they could act as novel biomarkers for the diagnosis and treatment of TNBC.
Insights
Triple-negative breast cancer (TNBC) molecular mechanisms were studied using gene expression data. Cyclin CDK1, CCNB1, and CCNA2 were identified as key genes overexpressed in TNBC, correlating with poor survival outcomes.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Triple-negative breast cancer (TNBC) is a significant cause of cancer-related mortality in females worldwide.
- The underlying molecular mechanisms of TNBC require further elucidation.
Purpose of the Study:
- To identify differentially expressed genes (DEGs) in TNBC compared to normal tissues.
- To investigate the prognostic significance of identified DEGs in TNBC patients.
Main Methods:
- Analysis of public microarray and high-throughput sequencing data from the GEO database.
- Functional and pathway enrichment analysis of DEGs using Funrich software.
- Construction of a protein-protein interaction (PPI) network and identification of hub genes using STRING and Cytoscape.
- Survival analysis (overall survival and progression-free survival) using the KM plotter.
Main Results:
- Identified 1638 DEGs, including 984 upregulated and 654 downregulated genes.
- Cyclin-dependent kinase 1 (CDK1), cyclin B1 (CCNB1), and cyclin A2 (CCNA2) emerged as top hub genes in the PPI network and were enriched in the cell cycle pathway.
- Overexpression of CDK1, CCNB1, CCNA2, and PLK1 correlated with worse overall survival in breast cancer.
- High CCNB1 expression was associated with worse progression-free survival in TNBC (HR=1.42, P=0.028).
Conclusions:
- CDK1, CCNB1, and CCNA2 are significantly overexpressed in TNBC.
- These cyclins demonstrate potential as novel biomarkers for TNBC diagnosis and therapeutic targeting.
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