High BIRC7 Expression Might Be an Independent Prognostic Indicator of Poor Recurrence-Free Survival in Patients With Prostate Cancer

Background: BIRC7, which encodes Baculoviral inhibitor of apoptosis (IAP) repeat-containing protein 7, is an oncogene in multiple types of cancer. In this study, we examined the association between BIRC7 expression and the clinicopathological characteristics of prostate cancer, the independent prognostic value of BIRC7 in terms of recurrence-free survival, and the molecular mechanisms of its dysregulation.

Methods: Data mining was performed using data from The Cancer Genome Atlas. The patients were divided into high and low BIRC7 expression groups according to the Youden index determined by receiver operating characteristic curves for recurrence. Subgroup analysis was performed according to T stages and Gleason score.

Results: BIRC7 was significantly upregulated in prostate cancer tissues (N = 497) than in normal prostate tissues (N = 52). High BIRC7 expression group had lower ratios of overall response rate and medium-grade (Gleason score 6-7) tumors and higher proportions of nodal invasion and recurrence after surgery. Although Kaplan-Meier curves showed that high BIRC7 expression was generally associated with poor recurrence-free survival, the following subgroup analysis only confirmed the association in T3/T4 and medium-grade tumors. Multivariate analysis showed that BIRC7 expression was not an independent indicator of recurrence-free survival in T2 or high-grade tumors, but was independently associated with poor recurrence-free survival in T3/T4 tumors (hazard ratio: 4.249, 95% confidence interval: 1.563-11.546, P = .005) and in medium-grade tumors (hazard ratio: 6.041, 95% confidence interval: 1.763-20.703, P = .004). DNA amplification was associated with significantly upregulated BIRC7 expression. There was also a weak negative correlation between BIRC7 expression and its DNA methylation (Pearson r = -0.23).

Conclusion: Based on these findings, we infer that BIRC7 upregulation might serve as a valuable biomarker of increased recurrence risk in advanced T stages and medium-grade prostate cancer. Its expression is at least regulated by both copy number alteration and DNA methylation.