Expression of bone morphogenetic protein-2 and -7 in urinary bladder cancer predicts time to tumor recurrence

Abstract

Introduction: Urinary bladder cancer patients who have undergone transurethral resection of bladder tumor (TURBT) are at risk of recurrence. This study aims to correlate the level of bone morphogenetic protein (BMP) expression with urothelial carcinoma invasiveness, TNM stage and time to recurrence after TURBT.

Material and methods: In 33 specimens of healthy transitional epithelium and 42 of urothelial carcinoma, BMP2, BMP4 and BMP7 expression was determined by real-time polymerase chain reaction. Patients who underwent TURBT were followed up for 1 year.

Results: BMP2 and BMP7 were downregulated in infiltrating urothelial carcinoma, the relative expression being 0.76 (p = 0.04) and 0.28 (p = 0.025) respectively, while BMP4 was downregulated in non-invasive tumors. High expression of BMP2 and BMP7 correlated with prolonged time to recurrence (log-rank: p = 0.01 and p = 0.03 respectively).

Conclusions: Low expression of BMP2 and BMP7 is associated with shorter time to recurrence. The BMP expression levels are not indicative of tumor stage.

Keywords: bone morphogenetic protein 2; bone morphogenetic protein 4; bone morphogenetic protein 7; urinary tract epithelium; urothelial carcinoma.

Figure 1

The BMP2, BMP4 and BMP7 expression level relative to healthy transitional epithelium (TE). Comparison between healthy urothelial transitional tissue (n = 33, empty bars) and urothelial carcinoma samples (n = 42, black bars) (A), BMP2 (B), BMP4 (C) and BMP7 (D) relative expression level in healthy TE (n = 33, TE), non-invasive urothelial carcinoma (n = 24, niUC) and invasive urothelial carcinoma (n = 18, iUC) Significance of the difference is indicated as follows *p < 0.05; **p < 0.01; Error bars represent SEM.

Figure 2

BMP2 (A), BMP4 (B), BMP7 (C) expression at different TNM stages (pTa (n = 24), pT1–2 (n = 8), pT3–4 (n = 10)). Presented values are relative to mean of normal transitional epithelium Horizontal lines represent median. r – Spearman's rank correlation coefficient between gene expression and TNM stages; p – statistical significance.

Figure 3

Kaplan-Meier estimators for UC recurrence probability for all analyzed subjects (n = 24) (A), BMP2 (B), BMP4 (C), BMP7 (D) Kaplan-Meier estimators for UC recurrence probability respectively Dashed line – low BMP expression, solid line – medium/high BMP expression. Significance of the differences is indicated (logrank test). +Censored data.