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Performing Data Mining And Integrative Analysis Of Biomarker in Breast Cancer Using Multiple Publicly Accessible Databases
Published on: May 17, 2019
Integrated Bioinformatics Analysis for the Screening of Hub Genes and Therapeutic Drugs in Androgen Receptor-Positive
Qiaonan Guo1, Pengjun Qiu1, Qingzhi Yao1
1Thyroid & Breast Surgery, The Second Affiliated Hospital of Fujian Medical University, 950 Donghai Street, Quanzhou, China.
Abstract:
As the most invasive and lethal subtype of breast cancer (BC), triple-negative breast carcinoma (TNBC) is of increasing interest. However, the androgen receptor (AR) still has an unclear role in TNBC. The current study is aimed at testing the diagnostic and therapeutic performance of novel biomarkers for AR-positive TNBC. The GSE76124 dataset was analyzed by combining WGCNA and other bioinformatics methods. Subsequently, function enrichment analysis was applied to identify the relationships between these differential expression genes (DEGs). Subsequently, the protein-protein interaction network was established, and the hub genes were identified by Cytoscape software. Eventually, the miRNA-hub gene modulate network was developed and the Drug-Gene Interaction Database (DGIdb) was applied to verify the potential drugs for AR-positive TNBC. In the current research, 88 DEGs in total were selected from the intersection of the purple module genes identified by WGCNA and limma package. TFF1, FOXA1, ESR1, AGR2, TFF3, AGR3, GATA3, XBP1, SPDEF, and TOX3 were selected as hub genes by the MCC method, which were all upregulated. The survival analysis suggested that TFF1 was the only one related to significant lower survival rate in TNBC. Ultimately, hsa-miR-520g-3p and hsa-miR-520h were found taking part in the regulation of TFF1, and 2 small molecules were identified as the potential targets for AR-positive TNBC treatment. As a result, our study suggested that hsa-miR-520g-3p, hsa-miR-520h, and TFF1 might have significant potential values for AR-positive TNBC diagnosis and prognosis prediction. TFF1, hsa-miR-520g-3, and hsa-miR-520h may serve as the novel therapeutic targets, and our findings offer further insights into the therapy of AR-positive TNBC.
Insights
This study identifies TFF1, hsa-miR-520g-3p, and hsa-miR-520h as potential biomarkers for diagnosing and predicting outcomes in androgen receptor-positive triple-negative breast cancer (AR+ TNBC). These molecules may also serve as novel therapeutic targets for AR+ TNBC.
Area of Science:
- Oncology
- Genomics
- Biomarker Discovery
Background:
- Triple-negative breast cancer (TNBC) is an aggressive subtype with limited targeted therapies.
- The role of the androgen receptor (AR) in TNBC remains incompletely understood.
- Identifying novel biomarkers for AR-positive TNBC (AR+ TNBC) is crucial for improving diagnosis and treatment.
Purpose of the Study:
- To investigate novel biomarkers for AR+ TNBC.
- To evaluate the diagnostic and therapeutic potential of these biomarkers.
- To explore potential therapeutic targets for AR+ TNBC.
Main Methods:
- Weighted Gene Co-expression Network Analysis (WGCNA) on the GSE76124 dataset.
- Differential gene expression analysis using the limma package.
- Protein-protein interaction network construction and hub gene identification using Cytoscape.
- miRNA-hub gene network analysis and drug-gene interaction verification.
Main Results:
- 88 differentially expressed genes (DEGs) were identified, with 10 hub genes (TFF1, FOXA1, ESR1, AGR2, TFF3, AGR3, GATA3, XBP1, SPDEF, TOX3) found to be upregulated.
- TFF1 was significantly associated with a lower survival rate in TNBC patients.
- hsa-miR-520g-3p and hsa-miR-520h were identified as regulators of TFF1.
- Two small molecules were identified as potential therapeutic targets for AR+ TNBC.
Conclusions:
- TFF1, hsa-miR-520g-3p, and hsa-miR-520h show promise as diagnostic and prognostic biomarkers for AR+ TNBC.
- These molecules represent potential novel therapeutic targets for AR+ TNBC.
- The findings provide insights into the therapeutic strategies for AR+ TNBC.

