Heparanase Expression in Colorectal Cancer and Its Relationship with Clinical Prognosis_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

XIAO Yi ¹ , FENG Yunlu ² , QIAN Jiaming ² , CHEN Yuanjia ² , LIN Guole ¹ , ZHANG Yuening ² , WU Bin ¹ , QIU Huizhong ¹

Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China;

Corresponding author：

Keywords：

Heparanase; Colorectal cancer; Prognosis

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Objective 　Heparanase can specifically cleave carbohydrate chains of heparan sulphate proteoglycans, which is an important component of the extracellular matrix. This study was designed to investigate the expression of heparanase in patients with colorectal cancer, and to analyze its relationships with progression of the cancer and clinical prognosis.
Methods 　Samples were collected from 36 patients with colorectal cancers from 2003 to 2004 in Peking Union Medical College Hospital, and were embeded by Paraffin and fresh-frozened. The expression of heparanase mRNA and its protein were measured by RT-PCR and immunohistochemistry. The relationships between these expressions and the clinicopathologic information (tumor invasion, tumor differentiation, lymph node involvement, accompanying with colorectal adenoma and 2-year survival) were also evaluated.
Results 　The expressions of heparanase mRNA in colorectal cancer (19/31， 61.3%) were significantly higher than those in normal colorectal tissues (6.5%). The overexpressions in normal tissues were positively correlated to the incidence of adenoma in patients with colorectal cancer （r=0.352， P=0.024）. The result of immunohistochemistry also showed that heparanase mainly expressed in the vascular endothelium within cancer tissues and the peripheral invased region outside cancer tissues. The 2-year disease-free-survival in patients with negative heparanase expression (88.9%) was higher than that with positive heparanase expression (50.0%), but there was no significant difference （P=0.078）.
Conclusion　 Heparanase overexpressed in colorectal cancer tissues, and thus it may take a role as an indicator for the formation and prognosis of colorectal cancer.

Citation： XIAO Yi,FENG Yunlu,QIAN Jiaming,CHEN Yuanjia,LIN Guole,ZHANG Yuening,WU Bin,QIU Huizhong. Heparanase Expression in Colorectal Cancer and Its Relationship with Clinical Prognosis. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2007, 14(4): 442-447. doi: Copy

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8.	Takaoka M, Naomoto Y, Ohkawa T, et al. Heparanase expression correlates with invasion and poor prognosis in gastric cancers [Ｊ]　. Lab Invest, 2003; 83(5)∶613.
9.	Xiao Y, Kleeff J, Shi X, et al. Heparanase expression in hepatocellular carcinoma and the cirrhotic liver [Ｊ]　. Hepatol Res, 2003; 26(3)∶192.
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13.	Friedmann Y, Vlodavsky I, Aingorn H, et al. Expression of heparanase in normal, dysplastic, and neoplastic human colonic mucosa and stroma. Evidence for its role in colonic tumorigenesis [Ｊ]　. Am J Pathol, 2000; 157(4)∶1167.
14.	Edovitsky E, Elkin M, Zcharia E, et al. Heparanase gene silencing, tumor invasiveness, angiogenesis, and metastasis [Ｊ]　. J Natl Cancer Inst， 2004; 96(16)∶1219.
15.	Sato T, Yamaguchi A, Goi T, et al. Heparanase expression in human colorectal cancer and its relationship to tumor angiogenesis, hematogenous metastasis, and prognosis [Ｊ]　. J Surg Oncol, 2004; 87(4)∶174.
16.	Wang ZN, Xu HM, Jiang L, et al. Positive association of Rh-oC gene overexpression with tumour invasion and lymphatic metastasis in gastric carcinoma [Ｊ]　. Chin Med J (Engl), 2005; 118(6)∶502.

1. 　Bernfield M, Gotte M, Park PW, et al. Functions of cell surface heparan sulfate proteoglycans [Ｊ]　. Annu Rev Biochem, 1999; 68∶729.
2. 　Sanderson RD. Heparan sulfate proteoglycans in invasion and metastasis [Ｊ]　. Semin Cell Dev Biol, 2001; 12(2)∶89.
3. 　Kleeff J, Ishiwata T, Kumbasar A, et al. The cell-surface heparan sulfate proteoglycan glypican-1 regulates growth factor action in pancreatic carcinoma cells and is overexpressed in human pancreatic cancer [Ｊ]　. J Clin Invest, 1998; 102(9)∶1662.
4. 　Elkin M, Ilan N, Ishai-Michaeli R, et al. Heparanase as mediator of angiogenesis: mode of action [Ｊ]　. FASEB J, 2001; 15(9)∶1661　.
5. 　Greene FL, Page DL, Fleming ID, et al. AJCC Cancer Staging Manual [M]　. 6th Edition. New York: Springer, 2002　∶113-119　.
6. 　Vlodavsky I, Friedmann Y, Elkin M, et al. Mammalian hepa-ranase: gene cloning, expression and function in tumor progression and metastasis [Ｊ]　. Nat Med, 1999; 5(7)∶793.
7. 　Koliopanos A, Friess H, Kleeff J, et al. Heparanase expression in primary and metastatic pancreatic cancer [Ｊ]　. Cancer Res, 2001; 61(12)∶4655.
8. 　Takaoka M, Naomoto Y, Ohkawa T, et al. Heparanase expression correlates with invasion and poor prognosis in gastric cancers [Ｊ]　. Lab Invest, 2003; 83(5)∶613.
9. 　Xiao Y, Kleeff J, Shi X, et al. Heparanase expression in hepatocellular carcinoma and the cirrhotic liver [Ｊ]　. Hepatol Res, 2003; 26(3)∶192.
10. 　Stadlmann S, Moser PL, Pollheimer J, et al. Heparanase-1 gene expression in normal, hyperplastic and neoplastic prostatic tissue [Ｊ]　. Eur J Cancer, 2003; 39(15)∶2229.
11. 　Hulett MD, Freeman C, Hamdorf BJ, et al. Cloning of mammalian heparanase, an important enzyme in tumor invasion and metastasis [Ｊ]　. Nat Med, 1999; 5(7)∶803.
12. 　Nobuhisa T, Naomoto Y, Ohkawa T, et al. Heparanase expression correlates with malignant potential in human colon cancer [Ｊ]　. J Cancer Res Clin Oncol, 2005; 131(4)∶229.
13. 　Friedmann Y, Vlodavsky I, Aingorn H, et al. Expression of heparanase in normal, dysplastic, and neoplastic human colonic mucosa and stroma. Evidence for its role in colonic tumorigenesis [Ｊ]　. Am J Pathol, 2000; 157(4)∶1167.
14. 　Edovitsky E, Elkin M, Zcharia E, et al. Heparanase gene silencing, tumor invasiveness, angiogenesis, and metastasis [Ｊ]　. J Natl Cancer Inst， 2004; 96(16)∶1219.
15. 　Sato T, Yamaguchi A, Goi T, et al. Heparanase expression in human colorectal cancer and its relationship to tumor angiogenesis, hematogenous metastasis, and prognosis [Ｊ]　. J Surg Oncol, 2004; 87(4)∶174.
16. 　Wang ZN, Xu HM, Jiang L, et al. Positive association of Rh-oC gene overexpression with tumour invasion and lymphatic metastasis in gastric carcinoma [Ｊ]　. Chin Med J (Engl), 2005; 118(6)∶502.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Heparanase Expression in Colorectal Cancer and Its Relationship with Clinical Prognosis

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