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.The Breast Cancer Gene-Expression Miner v4.1 (bc-GenExMiner v4.1, http://bcgenex.centregauducheau.fr/BC-GEM), an open access database of published annotated genomics data, was utilized to analyze the relevance between BIRC5 and specific clinicopathological features of breast cancer [16,17]. Association between BIRC5 and metastatic relapse event was assessed using the prognostic module, and correlation of BIRC5 and co-expressed cell-division cycle protein 20 (CDC20) was evaluated using the correlation module.
UCSC XenaThe UCSC Xena browser (http://xena.ucsc.edu/) was used to analyze the TCGA Breast Cancer data using the level 3 data. The heatmap and correlation between BIRC5 and CDC20 were then constructed.
Kaplan-Meier PlotterThe Kaplan-Meier Plotter (http://kmplot.com/analysis/), a web tool capable to check the effect of 54675 genes on survival using 5143 clinical breast cancer samples, was applied to show the prognostic value of BIRC5 in relapse-free survival, overall survival, and distant metastasis-free survival [18]. The hazard ratio (HR) with 95% confidence interval (CI), and log-rank P-value were calculated automatically.