Abstract
Breast cancer (BC) is the most common malignancy in female, but the role of androgen receptor (AR) in triple-negative breast cancer (TNBC) is still unclear. This study aimed to exam the performance of innovative biomarkers for AR positive TNBC in diagnosis and therapies. Four datasets (GSE42568, GSE45827, GSE54002 and GSE76124) were analyzed by bioinformatic methods and the differential expression genes (DEGs) between the AR positive TNBC tissues and normal tissues were firstly identified by limma package and Venn diagrams. Next, Gene Ontologies (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed to explore the relationship between these DEGs. Then, the Protein-protein interaction (PPI) network was constructed. CytoHubba and bioinformatic approaches including Molecular Complex Detection (MCODE), Gene Expression Profiling Interactive Analysis (GEPIA), the Kaplan-Meier (KM) plotter and The Human Pro-tein Atlas (THPA) were used to identify the hub genes. Lastly, a miRNA-hub-gene regulatory axis was constructed by use of Target Scan database and ENCORI database. As a result, a total of 390 common DEGs were identified, including 250 up-regulated and 140 down-regulated. GO and KEGG enrichment analysis showed that the up-regulated DEGs were mostly enriched in the cell division, mitotic nuclear division, nucleosome, midbody, protein heterodimerization activity, cadherin binding involved in cell-cell adhesion, systemic lupus erythematosus and alcoholism, while the down-regulated DEGs were mainly enriched in carbohydrate metabolic process, extracellular space, extracellular region, zinc ion binding and microRNAs in cancer. Then, 13 hub genes (CCNB2, FOXM1, HMMR, MAD2L1, RRM2, TPX2, TYMS, CEP55, AURKA, CCNB1, CDK1, TOP2A, PBK) were selected. The survival analysis revealed that only CCNB1 was associated with significantly poor survival (P <0.05) in TNBC patients. Finally, we found that hsa-miR-3163 took part in the regulation of CCNB1 and constructed a potential hsa-miR-3163-CCNB1 regulatory axis. The results of current study suggest that CCNB1 and hsa-miR-3163 may serve as highly potential prognostic markers and therapeutic targets for AR positive TNBC. Our findings may make contributions to the diagnosis and therapies of AR positive TNBC.
Highlights
According to the latest cancer statistic, breast cancer is the most common malignant tumor in females, being the most important cause of cancer death in many countries [1,2,3]
triple-negative breast cancer (TNBC) is a special subtype of breast cancer defined as short of expression of the estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) [4]
TNBC has been subdivided into four categories: luminal androgen receptor (LAR), mesenchymal (MES), basal-like immunosuppressed (BLIS), and basal-like immune activated (BLIA) [5]
Summary
According to the latest cancer statistic, breast cancer is the most common malignant tumor in females, being the most important cause of cancer death in many countries [1,2,3]. TNBC is a special subtype of breast cancer defined as short of expression of the estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) [4]. AR is a transcription factor widely involved in the development of breast, and its importance is self-evident [6]. 10–43% of TNBC, being involved in the invasion and metastasis of malignant tumor [7, 8]. It is urgent to understand the molecular mechanisms of AR positive TNBC progression to identify the potential biomarkers and therapeutic targets
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