High BTBD7 Expression Positive Correlated with SLUG Predicted Poor Prognosis in Hormone Receptor Negative Breast Cancer

Abstract There is a poor prognosis of metastasis in hormone receptor negative breast cancer (HRNBC), including triple-negative breast cancer (TNBC) and HER-2 overexpression breast cancer. Recent studies have indicated that BTB/POZ domain-containing protein 7 (BTBD7) regulates SLUG which is a key EMT (epithelial-mesenchymal transformation)-associated protein. The role of BTBD7 in HRNBC, however, has not been identified. In this study, The Cancer Genome Atlas (TCGA) was used to identify BTBD7 mRNA expression in breast cancer. In addition, GO and Metascape were used to identify differentially expressed genes. Immunohistochemical staining were applied to determine the protein expression of Btbd7 and Slug in paraffin-embedded samples from 144 HRNBC patients and 30 benign lesion patients. In cancer tissue, 64.9% in TNBC and 70.0% in HER-2+ overexpression breast cancer of Btbd7 protein was expressed when compared with a 20% expression in benign lesion tissues. Increased Btbd7 expression was further associated with larger tumor volume and poor TNM stages in HRNBC patients. Higher BTBD7 mRNA expression level was associated with shorter disease free survival (DFS) time from TCGA data. Higher Btbd7 protein expression in HRNBC tissue was associated with shorter DFS and OS time. Btbd7 protein expression significantly correlated with Slug expression in HRNBC tissue. Combining Btbd7 and Slug expression had a high predictive value for 3-year and 5-year DFS. As such, the positive expression of Btbd7 may contribute towards the development of breast cancer, specifically HRNBC via the up-regulation of Slug expression. Btbd7 was concluded to be an important predictor for the diagnosis of HRNBC patients.