Wu Bin-Wen, Li Dong-Feng, Ke Zun-Fu, Ma Dong, Li You-Jia, Gang Deng, Zheng Zhi-Gang, Zhang Kai-Jun, Zhang Ying-Hua
Division of Gastroenterology, Institute of Geriatrics, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, PR China.
Hepatogastroenterology. 2010 Nov-Dec;57(104):1510-4.
BACKGROUND/AIMS: Heparanase (HPA) influences tumourigenesis and tumour progression by various mechanisms, including angiogenesis. Cyclooxygenase-2 (COX-2) was strongly correlated with microvessel density, and that COX-2 expression is up-regulated by HPA in esophageal cancer. In this study, we examined the relationship between HPA expression and that of COX-2 in colon carcinoma. The aim of this study was to determine whether the expression of HPA is related to the angiogenesis in colorectal cancer and whether it could be involved in clinical behaviour of colon carcinoma.
HPA and COX-2 was analyzed with Immunohistochemistry and Western blot. Microvessels in colon carcinoma were examined by using anti-CD34 antibody. Statistical analysis was applied to test for the prognostic and diagnostic associations.
Immunohistochemistry revealed that HPA was expressed at low level in normal colonic mucosa (4/78, 5.1%), but at higher level in tumor tissues (63/78, 80.7%) and closely correlated with tumor lymph node metastasis (p < 0.05). This result was further confirmed by Western blot analysis. Furthermore, carcinomas with high HPA expression demonstrated high COX-2 expression and high MVD (microvesseldensity) labelled with CD34. In addition, mortality was higher in patients with HPA+ phenotype and HPA was an independent predictor of overall survival (p < 0.05).
Our findings indicated that HPA might be an important biomarker for malignant transformation and be involved in promoting colon carcinoma metastasis by increasing angiogenesis.
背景/目的：乙酰肝素酶（HPA）通过多种机制影响肿瘤发生和肿瘤进展，包括血管生成。环氧合酶-2（COX-2）与微血管密度密切相关，且在食管癌中HPA可上调COX-2表达。在本研究中，我们检测了结肠癌中HPA表达与COX-2表达之间的关系。本研究的目的是确定HPA表达是否与结直肠癌中的血管生成相关，以及它是否参与结肠癌的临床行为。
采用免疫组织化学和蛋白质印迹法分析HPA和COX-2。使用抗CD34抗体检测结肠癌中的微血管。应用统计学分析来检验预后和诊断相关性。
免疫组织化学显示，HPA在正常结肠黏膜中低表达（4/78，5.1%），但在肿瘤组织中高表达（63/78，80.7%），且与肿瘤淋巴结转移密切相关（p<0.05）。蛋白质印迹分析进一步证实了这一结果。此外，HPA高表达的癌组织显示COX-2高表达以及CD34标记的高微血管密度（MVD）。此外，HPA+表型患者的死亡率更高，且HPA是总生存的独立预测因子（p<0.05）。
我们的研究结果表明，HPA可能是恶性转化的重要生物标志物，并通过增加血管生成参与促进结肠癌转移。
