Abstract
Aims: Baculoviral inhibitor of apoptosis repeat containing 5 (BIRC5) plays vital roles in carcinogenesis by influencing cell division and proliferation and by inhibiting apoptosis. However, the prognostic significance of BIRC5 remains unclear in breast cancer.Methods: BIRC5 expression and methylation status were evaluated using the Oncomine and The Cancer Genome Atlas (TCGA) databases. The relevance between BIRC5 and different clinicopathological features as well as survival information was analyzed using the bc-GenExMiner database and Kaplan–Meier Plotter. BIRC5–drug interaction network was obtained using the Comparative Toxicogenomics Database.Results: Based on the results from databases and own hospital data, BIRC5 was higher expressed in different breast cancer subtypes compared with the matched normal individuals. Hormone receptors were negatively correlated with BIRC5 expression, whereas the Scarff–Bloom–Richardson (SBR) grade, Nottingham Prognostic Index (NPI), human epidermal growth factor receptor-2 (HER-2) status, basal-like status, and triple-negative status were positively related to BIRC5 level in breast cancer samples with respect to normal tissues. High BIRC5 expression was responsible for shorter relapse-free survival, worse overall survival, reduced distant metastasis free survival, and increased risk of metastatic relapse event. BIRC5–drug interaction network indicated that several common drugs could modulate BIRC5 expression. Furthermore, a positive correlation between BIRC5 andcell-division cycle protein 20 (CDC20) gene was confirmed.Conclusion: BIRC5 may be adopted as a promising predictive marker and potential therapeutic target in breast cancer. Further large-scale studies are needed to more precisely confirm the value of BIRC5 in treatment of breast cancer.
Highlights
Breast cancer is the most common malignancy among women worldwide [1,2]
Oncomine database revealed that Baculoviral inhibitor of apoptosis repeat containing 5 (BIRC5) was significantly higher expressed in breast cancer patients compared with the matched normal individuals (Figure 1A)
The Cancer Genome Atlas (TCGA) data analyzed by the Ualcan online tool confirmed that higher BIRC5 was expressed in breast cancer tissues than in normal tissues (Figure 1B, P
Summary
Breast cancer is the most common malignancy among women worldwide [1,2]. precise surgery and adjuvant systemic treatments including chemotherapeutic agents, radiotherapy, hormone therapy, and molecular targeting drugs greatly improve the overall outcome, the prognosis of breast cancer remains poor. The limitation of clinical, pathological, and molecular features in individualized tumor therapy urgently requires a novel approach to predict outcome and treatment response. Inactivation of nuclear export signal for BIRC5 may increase therapy response in head and neck cancer patients [8]. Both molecular suppression by gene editing approach and pharmacological inhibition by BIRC5 antagonist could reduce the growth, migration, and invasiveness of ovarian cancer cells [7]. Targeting BIRC5 in experimental models improves survival [11] Together, these findings indicate that BIRC5 may function as an oncogene, and as a promising predictive biomarker and potential therapeutic target in cancer [12]. The present work was carried out to validate the expression pattern, potential function, prognostic value, and drug interaction network of BIRC5 in breast cancer by performing bioinformatics analysis of several large online databases
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