[缺氧诱导因子-1α、硫酸乙酰肝素酶和血管内皮生长因子促进视网膜母细胞瘤的恶性进展]

[HIF-1alpha, HPSE and VEGF promote malignant progression of retinoblastoma].

作者信息

Wang Xiao-lei, Niu Ying-jun, Ma Jian-min

机构信息

Department of Ophthalmology, Affiliated Hospital of Medical College, Qingdao University, Qingdao 266021, China.

出版信息

Zhonghua Yan Ke Za Zhi. 2010 Feb;46(2):140-4.

PMID:20388348

Abstract

OBJECTIVE

To investigate the expression of heparanase (HPSE), hypoxia-inducible factor (HIF-1alpha) and their correlation with expression of vascular endothelial growth factor (VEGF) and microvessel density (MVD) in retinoblastoma.

METHODS

HIF-1alpha and VEGF were detected by SP immunohistochemical method in 34 cases of retinoblastoma and 10 cases of normal retina tissues. MVD was measured by anti-CD34. Eighteen samples of retinoblastoma tissues and ten samples of normal retina were examined for HPSE mRNA, HIF-1alpha mRNA, VEGF mRNA expression by RT-PCR. The correlation between HPSE, HIF-1alpha and VEGF expression, MVD and clinical and pathological characters were analyzed. The statistical methods are the measurement data using grouped quantitative data t test, variance analysis and q test; enumeration data compared with chi(2) test, Fisher test and rank sum test; correlation analysis using Spearman rank correlation analysis and the kappa test.

RESULTS

The positive expression rates of HIF-1alpha and VEGF were 58.8%, 64.7% higher in retinoblastoma than in normal retina's (chi(2) = 10.784, P < 0.05; chi(2) = 9.269, P < 0.05). Positive expression of HPSE, HIF-1alpha, VEGF mRNA were found in 55.6%, 44.4%, 72.2%. The expression of HIF-lalpha and VEGF in retinoblastoma were correlated with MVD (r = 0.664, P < 0.05; r = 0.590, P < 0.05). VEGF was correlated with HPSE and HIF-1alpha (Z = 2.350, P = 0.009; Z = 2.940, P = 0.002).

CONCLUSIONS

HPSE and HIF-1alpha can influence the expression of VEGF, an important angiogenesis factor. HPSE, HIF-1alpha and VEGF play a role in tumor angiogenesis and promote malignant progress of retinoblastoma.

摘要

目的

探讨乙酰肝素酶（HPSE）、缺氧诱导因子（HIF-1α）在视网膜母细胞瘤中的表达及其与血管内皮生长因子（VEGF）表达和微血管密度（MVD）的相关性。

方法

采用SP免疫组化法检测34例视网膜母细胞瘤组织及10例正常视网膜组织中HIF-1α和VEGF的表达，用抗CD34检测MVD。采用RT-PCR检测18例视网膜母细胞瘤组织及10例正常视网膜组织中HPSE mRNA、HIF-1α mRNA、VEGF mRNA的表达。分析HPSE、HIF-1α与VEGF表达、MVD及临床病理特征之间的相关性。统计学方法为计量资料采用分组定量资料t检验、方差分析和q检验；计数资料采用χ²检验、Fisher检验和秩和检验；相关性分析采用Spearman等级相关分析和kappa检验。

结果

视网膜母细胞瘤组织中HIF-1α和VEGF的阳性表达率分别为58.8%、64.7%，高于正常视网膜组织（χ² = 10.784，P < 0.05；χ² = 9.269，P < 0.05）。HPSE、HIF-1α、VEGF mRNA阳性表达率分别为55.6%、44.4%、72.2%。视网膜母细胞瘤组织中HIF-1α和VEGF的表达与MVD相关（r = 0.664，P < 0.05；r = 0.590，P < 0.05）。VEGF与HPSE和HIF-1α相关（Z = 2.350，P = 0.009；Z = 2.940，P = 0.002）。