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 phenotype 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.