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Cystatins in non-small cell lung cancer: Tissue levels, localization and relation to prognosis

På svenska

Author

  • Bernd Werle
  • Ulrike Schanzenbaecher
  • Tamara Turensek Lah
  • Eileen Ebert
  • Britta Juelke
  • Werner Ebert
  • Werner Fiehn
  • Klaus Kayser
  • Eberhard Spiess
  • Magnus Abrahamson
  • Janko Kos
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Summary, in English

Cystatins regulate tumour-associated cysteine proteases, however, their role in tumour progression is not clear yet. To assess their relevance in the progression of nonsmall cell lung cancer (NSCLC) the protein level, cysteine protease activity (CPI) and localization of type I (stefins A and B) and type H (C, E/M and F) cystatins were defined in tumours and control lung counterparts from 165 patients. The medians of CPI activity, stefins A and B were significantly greater in tumour than in lung tissue (2.1-fold, 1.7-fold, 1.2-fold, respectively, all p < 0.001). The median levels of cystatin C and cystatin E/M were lower in tumour tissue (0.9-fold, p=0.06; 0.6-fold, p < 0.01). In all the samples the levels of cystatin F were below the detection limit. Immunohistochemical analysis revealed the presence of all cystatins in tumour cells and infiltrated inflammatory cells such as macrophages and neutrophils. In univariate survival analysis patients with high levels of stefin A, stefin B and CPI activity exhibited a better survival probability (p=0.05, p=0.05, p < 0.01, respectively). In contrast, cystatins C and E/M provided no prognostic information. In multivariate analysis the most powerful predictor of survival was the pTNM stage (p < 0.0001; RR 3.5), followed by stefin A, stefin B and CPI activity (all p=0.03; RR 1.5). Our results suggest that only stefins A and B, i.e. type I cystatins, are up-regulated in lung tumours and thus able to counteract harmful tumour-associated proteolytic activity. As biological markers they may add independent prognostic information for better assessment of low- and high-risk patients with NSCLC.

Publishing year

2006

Language

English

Pages

647-655

Publication/Series

Oncology Reports

Volume

16

Issue

4

Document type

Journal article

Publisher

Spandidos Publications

Topic

  • Cancer and Oncology

Keywords

  • cancer
  • non-small cell lung
  • cathepsin
  • cysteine protease
  • stefin
  • cystatin
  • prognosis

Status

Published

ISBN/ISSN/Other

  • ISSN: 1791-2431