Galectin-3 expression is associated with bladder cancer progression and clinical outcome.
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.
Canesin
Giacomo
G
Tumor Markers Group, Molecular Pathology Program, Spanish National Cancer Center, Madrid, Spain.
Gonzalez-Peramato
Pilar
P
Palou
Joan
J
Urrutia
Manuel
M
Cordón-Cardo
Carlos
C
Sánchez-Carbayo
Marta
M
D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D018450:Disease Progression; D037502:Galectin 3 / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D046888:Tissue Array Analysis; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured; D001743:Urinary Bladder / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
D014408:Biomarkers, Tumor; D037502:Galectin 3; D012333:RNA, Messenger
Proc Natl Acad Sci U S A. 1996 Jun 25;93(13):6737-42
8692888
Methods Enzymol. 2006;417:273-89
17132511
CA Cancer J Clin. 2009 Jul-Aug;59(4):225-49
19474385
Clin Cancer Res. 2000 Apr;6(4):1389-93
10778968
J Biol Chem. 1994 Aug 19;269(33):20807-10
8063692
Apoptosis. 2005 Mar;10(2):267-75
15843888
Biochim Biophys Acta. 1999 Dec 6;1473(1):172-85
10580137
Curr Med Chem. 2006;13(29):3513-27
17168720
J Mol Med (Berl). 1998 May;76(6):402-12
9625297
Int J Cancer. 2007 Jun 1;120(11):2331-8
17304502
J Cell Biol. 2000 Dec 11;151(6):1235-46
11121438
J Cancer Res Clin Oncol. 2001;127(6):375-86
11414198
Int J Cancer. 1999 Feb 19;84(1):39-43
9988230
Biochim Biophys Acta. 2002 Sep 19;1572(2-3):285-93
12223276
Int J Oncol. 2004 Oct;25(4):983-92
15375548
J Exp Clin Cancer Res. 2001 Jun;20(2):301-4
11484992
Semin Oncol. 2007 Apr;34(2):75-84
17382791
Int J Cancer. 2000 Jul 20;89(4):361-7
10956411
Cancer Res. 2005 Sep 1;65(17):7546-53
16140916
Int J Cancer. 1990 Nov 15;46(5):871-7
2228316
J Neurosci Res. 2000 Mar 15;59(6):722-30
10700009
J Clin Oncol. 2006 Feb 10;24(5):778-89
16432078
Oncol Rep. 2008 Dec;20(6):1403-8
19020721
J Cell Biochem. 2004 Jan 1;91(1):118-24
14689585
Am J Clin Pathol. 1999 May;111(5):623-31
10230352
Cancer Res. 1997 Dec 1;57(23):5272-6
9393748
Genes Chromosomes Cancer. 2003 Jun;37(2):159-64
12696064
Technol Cancer Res Treat. 2006 Feb;5(1):67-72
16417404
Cancer Res. 2006 Mar 15;66(6):3114-9
16540661
Cancer. 1995 Jun 15;75(12):2818-26
7773932
Int J Oncol. 1998 Jun;12(6):1287-90
9592187
Int J Oncol. 1999 Jul;15(1):143-8
10375607
Methods Enzymol. 2006;417:256-73
17132510
J Biol Chem. 2002 May 3;277(18):15819-27
11839755
Cancer. 1999 Jun 1;85(11):2475-84
10357421
Hum Pathol. 2005 Aug;36(8):908-14
16112008
Biochimie. 2001 Jul;83(7):667-76
11522396
Anticancer Res. 2006 Mar-Apr;26(2B):1369-76
16619546
Nat Rev Cancer. 2005 Jan;5(1):29-41
15630413
J Pathol. 1996 May;179(1):43-8
8691344