Galectin-3 expression is associated with bladder cancer progression and clinical outcome

Abstract

Galectin-3 belongs to a family of carbohydrate-binding proteins whose function is not fully characterized. However, it is believed to play a role in adhesion, proliferation and apoptosis in solid tumors. We aimed at investigating galectin-3 expression in bladder cancer. Galectin-3 expression was assessed by transcript profiling (U133A arrays) in a series or frozen bladder tumors (n = 105). Immunohistochemistry was performed on tissue arrays containing bladder tumors (n = 389) to evaluate associations of protein expression patterns of galectin-3 with proliferation (Ki67), apoptosis (apopdetek), bcl-2, and clinicopathologic variables. Galectin-3 protein levels were then quantified in 160 urinary specimens of bladder cancer patients and controls by enzymeimmunoanalysis. Galectin-3 gene expression levels increased in invasive tumours as compared with non-muscle invasive lesions (p = 0.001) and were associated with poor survival in patients with advanced disease (p = 0.03). Protein expression patterns also correlated galectin-3 with tumor stage (p < 0.001), grade (p = 0.03), Ki67 and apopdetek (p < 0.001), and overall survival in patients with T1G3 tumors (p < 0.001). Furthermore, galectin-3 urinary levels segregated bladder cancer patients from controls with high diagnostic accuracy (AUC = 0.7). Independent series of bladder tumors showed that transcript and protein levels of galectin-3 were differentially expressed along bladder cancer progression. Urinary protein levels served to identify bladder cancer patients. These observations suggest a role for galectin-3 as a biomarker for bladder cancer diagnostics, staging, and outcome prognosis.