Overexpression of GABRP gene in triple negative breast cancer: Molecular mechanisms and interpretation

Abstract

Background: Triple-negative breast cancer (TNBC) is a heterogeneous disease that characterized by aggressiveness features with increased metastasis and poor clinical prognosis. However, the molecular mechanisms underlying this highly malignant pheno-type are still poorly understood. It has been well documented that the dysregulation of neural genes is profoundly implicated in cancer development and metastasis. Objectives: In the present study, the expression level of GABA receptor π subunit (GABRP) as the most up-regulated gene in TNBC and a hub node in the co-expression network were investigated. Methods: In this study, the importance of GABRP as the most up-regulated gene in TNBC was discovered through integrative analysis of multiple microarray expression datasets, containing about 1000 samples. Furthermore, the co-expression network analysis was constructed based on the up-regulated genes. Quantitative Real-time polymerase chain reaction (qRT-PCR) was used to evaluate of the GABRP expression in 50 TNBC compared to 33 non-TNBC tumors. Results: According to the bioinformatics analysis, GABRP occupies a key position in the co-expression network which is mainly enriched in the nervous systems development. The qRT-PCR results indicated that up-regulation of GABRP was highly concordant with integrative analysis findings. Moreover, the receiver operating characteristic (ROC) curve analysis revealed that GABRP can be a potential biomarker to distinguish TNBC from non-TNBC samples. Conclusions: Our study revealed that up-regulation of GABRP is among the most remarkable molecular signature in TNBC and may play a critical role in tumorigenesis. The results may provide a deeper insight into molecular mechanisms underlying the brain metastasis in TNBC tumors and propose the potential targets for therapeutic interventions.