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Published on: October 11, 2018
Integrative Bioinformatics Analysis Reveals CHEK1 and UBE2C as Luminal A Breast Cancer Subtype Biomarkers
Daowu Yu1, Shengwei Liu1, Yijun Chen1
1Yongchuan Hospital of Chongqing Medical University, Chongqing, China.
Abstract:
In light of the limited number of targetable oncogenic drivers in breast cancer (BRCA), it is important to identify effective and druggable gene targets for the treatment of this devastating disease. Herein, the GSE102484 dataset containing expression profiling data from 683 BRCA patients was re-analyzed using weighted gene co-expression network analysis (WGCNA). The yellow module with the highest correlation to BRCA progression was screened out, followed by functional enrichment analysis and establishment of a protein-protein interaction (PPI) network. After further validation through survival analysis and expression evaluation, CHEK1 and UBE2C were finally identified as hub genes related to the progression of BRCA, especially the luminal A breast cancer subtype. Notably, both hub genes were found to be dysregulated in multiple types of immune cells and closely correlated with tumor infiltration, as revealed by Tumor Immune Estimation Resource (TIMER) along with other bioinformatic tools. Construction of transcription factors (TF)-hub gene network further confirmed the existence of 11 TFs which could regulate both hub genes simultaneously. Our present study may facilitate the invention of targeted therapeutic drugs and provide novel insights into the understanding of the mechanism beneath the progression of BRCA.
Insights
Researchers identified CHEK1 and UBE2C as key genes driving breast cancer (BRCA) progression, particularly in luminal A subtypes. These genes are linked to immune cell dysregulation and tumor infiltration, offering potential new therapeutic targets.
Area of Science:
- Oncology
- Genomics
- Bioinformatics
Background:
- Limited targetable oncogenic drivers exist for breast cancer (BRCA).
- Identifying novel, druggable gene targets is crucial for effective BRCA treatment.
Purpose of the Study:
- To re-analyze gene expression data to identify novel hub genes associated with BRCA progression.
- To investigate the role of identified hub genes in immune cell infiltration and patient survival.
Main Methods:
- Weighted gene co-expression network analysis (WGCNA) on the GSE102484 dataset (683 BRCA patients).
- Functional enrichment analysis, protein-protein interaction (PPI) network construction.
- Survival analysis, expression evaluation, and analysis using Tumor Immune Estimation Resource (TIMER).
Main Results:
- The yellow module showed the highest correlation with BRCA progression.
- CHEK1 and UBE2C were identified as hub genes significantly related to BRCA progression, especially in luminal A subtype.
- Both hub genes were dysregulated in immune cells and correlated with tumor infiltration; 11 transcription factors regulating both genes were identified.
Conclusions:
- CHEK1 and UBE2C are potential therapeutic targets for breast cancer.
- These findings provide insights into BRCA progression mechanisms and immune cell involvement.
- The study facilitates the development of targeted therapies for breast cancer.
