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Expression of heparanase and its clinical significance in human non-small cell lung cancer

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Chinese Journal of Cancer Research

Abstract

Objective: To explore the expression and significance of heparanase in non-small cell lung cancer (NSCLC) regarding prognosis and clinicopathological parameters. Methods: The expression of heparanase was assessed using immunohistochemistry staining and Western blot in 122 paraffin-embedded specimens and 38 freshly taken tissues. The relationship between heparanase expression and the clinicopathological factors was analyzed by Chi-square test, multivariate analysis and Kaplan-Meier method. Results: In the immunoreactive cells, staining was mainly located in cytoplasma and membrane. Human heparanase was highly expressed in lung cancer tissue (78.7%, 96/122) while negative in epithelia of normal lung tissues. The level of heparanase was remarkably higher in NSCLC than that in normal tissue (P=0.043). Expression of heparanase significantly correlated with TNM stage (P=0.025), lymphatic metastasis (P=0.002) and vascular invasion (P=0.0003). The patients with positive heparanase expression had a significantly shorter survival than those with negative heparanase expression (P=0.0006). In multivariate analysis, only p-TNM stage, lymphatic metastasis and vascular invasion could be considered as prognostic factors. Conclusion: Elevated level of heparanase in human non-small cell lung cancer tissues correlates with the TNM stage, invasion, metastasis and prognosis. However, heparanase expression is not an independent prognostic factor.

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References

  1. Voldavsky I, Friedmann Y, Elkin M, et al. Mammalian heparanase: gene cloning, expression and function in tumor progression and metastasis [J]. Nat Med 1999; 5:793–802.

    Article  Google Scholar 

  2. Hulett MD, Freeman C, Hamdorf BJ, et al. Cloning of mammalian heparanase, an important enzyme in tumor invasion and metastasis [J] Nat Med 1999; 5:803–9.

    Article  PubMed  CAS  Google Scholar 

  3. Fairbanks MB, Mildner AM, Leone JW, et al. Processing of the human heparanase precursor and evidence that the active enzyme is a heterodimer [J]. J Biol Chem 1999; 274:29587–90.

    Article  PubMed  CAS  Google Scholar 

  4. Friedmann Y, Vlodavsky I, Aingorn H, et al. Expression of heparanase in normal, dysplastic and neoplastic human colonic mucosa and stroma [J]. Am J Pathol 2000; 157:1167–75.

    PubMed  CAS  Google Scholar 

  5. Rohloff J, Zinke J, Schoppmeyer K, et al. Heparanase expression is a prognostic indicator for postoperative survival in pancreatic adenocarcinoma [J]. Br J Cancer 2002; 86:1270–5.

    Article  PubMed  CAS  Google Scholar 

  6. Maxhimer JB, Quiros RM, Stewart R, et al. Heparanase-1 expression is associated with the metastatic potential of breast cancer [J]. Surgery 2002; 132:326–33.

    Article  PubMed  Google Scholar 

  7. Endo K, Maejara U, Baba H, et al. Heparanase gene expression and metastatic potential in human gastric cancer [J]. Anticancer Res 2001; 21:3365–9.

    PubMed  CAS  Google Scholar 

  8. Tang W, Nakamura Y, Tsujimoto M, et al. Heparanase: a key enzyme in invasion and metastasis of gastric carcinoma [J]. Mod Pathol 2002; 15:593–8.

    Article  PubMed  Google Scholar 

  9. Takaoka M, Naomoto Y, Ohkawa T, et al. Heparanase expression correlates with invasion and poor prognosis in gastric cancers [J]. Lab Invest 2003; 83:613–22.

    PubMed  CAS  Google Scholar 

  10. Mikami S, Ohashi K, Usui Y, et al. Loss of syndecan-1 and increased expression of heparanase in invasive esophageal carcinomas [J]. Jpn J Cancer Res 2001; 92:1062–73.

    PubMed  CAS  Google Scholar 

  11. Kuniyasu H, Chihara Y, Kubozoe T, et al. Co-expression of CD44v3 and heparanase is correlated with metastasis of human colon cancer [J]. Int J Mol Med 2002; 10:333–7.

    PubMed  Google Scholar 

  12. Kim AW, Xu X, Hollinger EF, et al. Human heparanase-1 gene expression in pancreatic adenocarcinoma [J]. J Gastrointest Surg 2002; 6:167–72.

    Article  PubMed  Google Scholar 

  13. Koliopanos A, Friess H, Kleeff J, et al. Heparanase expression in primary and metastatic pancreatic cancer [J]. Cancer Res 2001; 61:4655–9.

    PubMed  CAS  Google Scholar 

  14. Gohji K, Okamoto M, Kitazawa S, et al. Heparanase protein and gene expression in bladder cancer [J]. J Urol 2001; 166:1286–90.

    Article  PubMed  CAS  Google Scholar 

  15. Gohji K, Hirano H, Okamoto M, et al. Expression of three extracellular matrix degradative enzyme in bladder cancer [J]. Int J Cancer 2001; 95:295–301.

    Article  PubMed  CAS  Google Scholar 

  16. Kurokawa H, Katsube K, Podyma KA, et al. Heparanase and tumor invasion patterns in human oral squamous cell carcinoma xenografts [J]. Cancer Sci 2003; 94:277–85.

    Article  PubMed  CAS  Google Scholar 

  17. Ikeguchi M, Ueta T, Yamane Y, et al. Quantitative analysis of heparanase messenger RNA expression in hepatocellular carcinoma [J]. J Surg Oncol 2002; 81:148–54.

    Article  PubMed  CAS  Google Scholar 

  18. Zhang YL, Fu ZR, Ding GS, et al. Expression of heparanase mRNA and its clinical significance in primary hepatocellular carcinoma [J]. Clin J Oncol 2003; 25:359–61.

    CAS  Google Scholar 

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Correspondence to Qiu Xue-shan.

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Foundation item: This work was supported by the National Natural Sciences Foundation of China (No. 30170409) and the Scientific Research Foundation of Liaoning Education Office (No. 20122178).

Biography: HAN Yu-chen (1969–), female, doctor of medicine, associate professor, Department of Pathology, China Medical University, majors in tumor pathology.

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Han, Yc., Li, Sy., Yu, M. et al. Expression of heparanase and its clinical significance in human non-small cell lung cancer. Chin. J. Cancer Res. 17, 207–212 (2005). https://doi.org/10.1007/s11670-005-0042-1

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  • DOI: https://doi.org/10.1007/s11670-005-0042-1

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