Canesin Giacomo, Gonzalez-Peramato Pilar, Palou Joan, Urrutia Manuel, Cordón-Cardo Carlos, Sánchez-Carbayo Marta
Tumor Markers Group, Molecular Pathology Program, Spanish National Cancer Center, Madrid, Spain.
Tumour Biol. 2010 Aug;31(4):277-85. doi: 10.1007/s13277-010-0033-9. Epub 2010 Apr 17.
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.
半乳糖凝集素-3属于一类碳水化合物结合蛋白家族，其功能尚未完全明确。然而，据信它在实体瘤的黏附、增殖和凋亡过程中发挥作用。我们旨在研究半乳糖凝集素-3在膀胱癌中的表达情况。通过转录谱分析（U133A芯片）对一系列冷冻膀胱肿瘤（n = 105）评估半乳糖凝集素-3的表达。对包含膀胱肿瘤的组织芯片（n = 389）进行免疫组织化学检测，以评估半乳糖凝集素-3的蛋白表达模式与增殖（Ki67）、凋亡（apopdetek）、bcl-2以及临床病理变量之间的关联。随后通过酶免疫分析对160例膀胱癌患者及对照的尿液标本中的半乳糖凝集素-3蛋白水平进行定量。与非肌层浸润性病变相比，浸润性肿瘤中半乳糖凝集素-3基因表达水平升高（p = 0.001），且与晚期疾病患者的不良生存相关（p = 0.03）。蛋白表达模式也显示半乳糖凝集素-3与肿瘤分期（p < 0.001）、分级（p = 0.03）、Ki67和apopdetek（p < 0.001）以及T1G3肿瘤患者的总生存相关（p < 0.001）。此外，尿液中半乳糖凝集素-3水平能以较高的诊断准确性区分膀胱癌患者与对照（曲线下面积 = 0.7）。独立的膀胱肿瘤系列研究表明，半乳糖凝集素-3的转录和蛋白水平在膀胱癌进展过程中存在差异表达。尿液蛋白水平有助于识别膀胱癌患者。这些观察结果提示半乳糖凝集素-3可作为膀胱癌诊断、分期及预后的生物标志物。
