Integrated Bioinformatics Analysis for the Screening of Hub Genes and Therapeutic Drugs in Androgen Receptor-Positive TNBC.

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.