Expression of galectin-3 involved in prognosis of patients with hepatocellular carcinoma

被引:75
作者
Matsuda, Yasunori [1 ]
Yamagiwa, Yoko [1 ]
Fukushima, Koji [1 ]
Ueno, Yoshiyuki [1 ]
Shimosegawa, Tooru [1 ]
机构
[1] Tohoku Univ, Grad Sch Med, Div Gastroenterol, Aoba Ku, Sendai, Miyagi 9808574, Japan
基金
日本学术振兴会;
关键词
galectin-3; hepatocellular carcinoma; prognosis; tumor progression;
D O I
10.1111/j.1872-034X.2008.00387.x
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Aims:Galectins are multifunctional lectins binding to the beta-galactoside of glycoproteins that affect diverse physiological and pathophysiological processes such as development, inflammation and tumor growth. In hepatocellular carcinoma (HCC), the over-expression of galectin-1, 3, and 4 has been reported, although their function and correlation with tumor progression remain unknown. Thus, we aimed to assess the role of galectin-3 during HCC progression. Methods: Specimens were obtained during curative operations and used for immunohistochemical analysis of galectin-3 (n = 52), and statistically assessed for correlations with the clinical profiles and the prognoses of the patients. The serum galectin-3 levels from the patients with liver diseases including HCC were assessed by ELISA. Results: In total, galectin-3 expression was found in 34 of 52 tumors (65%) and was statistically correlated with histological differentiation and vascular invasion. Kaplan-Meier's analysis showed that patients with galectin-3 expression tended to relapse in the earlier phase and had worse overall survival. In particular, a higher expression rate of nuclear galectin-3 showed a markedly worse prognosis, and it was independent in the multivariate analysis for overall survival. Serum galectin-3 levels were significantly increased in HCC compared with chronic liver disease. The sensitivity and specificity of galectin-3 were equivalent to alpha-fetoprotein and Vitamin K absence or antagonist II, and the combination of HCC biomarkers with galectin-3 improved the diagnostic performance. Conclusions: Galectin-3 expression was involved in the tumor progression and related to the prognosis of HCC. Our observations suggested that galectin-3 could be a novel tumor marker and therapeutic target.
引用
收藏
页码:1098 / 1111
页数:14
相关论文
共 54 条
[1]   Dual activities of galectin-3 in human prostate cancer:: tumor suppression of nuclear galectin-3 vs tumor promotion of cytoplasmic galectin-3 [J].
Califice, S ;
Castronovo, V ;
Bracke, M ;
van den Brûle, F .
ONCOGENE, 2004, 23 (45) :7527-7536
[2]  
Castronovo V, 1996, J PATHOL, V179, P43, DOI 10.1002/(SICI)1096-9896(199605)179:1<43::AID-PATH541>3.0.CO
[3]  
2-N
[4]  
Chung EJ, 2002, MOL CELLS, V14, P382
[5]   Screening for hepatocellular carcinoma [J].
Collier, J ;
Sherman, M .
HEPATOLOGY, 1998, 27 (01) :273-278
[6]   Galectinomics: finding themes in complexity [J].
Cooper, DNW .
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, 2002, 1572 (2-3) :209-231
[7]   Galectin-3:: An open-ended story [J].
Dumic, J ;
Dabelic, S ;
Flögel, M .
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, 2006, 1760 (04) :616-635
[8]   Hepatocellular carcinoma: Epidemiology and molecular carcinogenesis [J].
El-Serag, Hashem B. ;
Rudolph, Lenhard .
GASTROENTEROLOGY, 2007, 132 (07) :2557-2576
[9]   Galectin-3 augments K-Ras activation and triggers a Ras signal that attenuates ERK but not phosphoinositide 3-kinase activity [J].
Elad-Sfadia, G ;
Haklai, R ;
Balan, E ;
Kloog, Y .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (33) :34922-34930
[10]  
Gillenwater A, 1996, HEAD NECK-J SCI SPEC, V18, P422, DOI 10.1002/(SICI)1097-0347(199609/10)18:5<422::AID-HED5>3.0.CO