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

In English

Författare

  • Bernd Werle
  • Ulrike Schanzenbaecher
  • Tamara Turensek Lah
  • Eileen Ebert
  • Britta Juelke
  • Werner Ebert
  • Werner Fiehn
  • Klaus Kayser
  • Eberhard Spiess
  • Magnus Abrahamson
  • Janko Kos
Visa allt

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.

Publiceringsår

2006

Språk

Engelska

Sidor

647-655

Publikation/Tidskrift/Serie

Oncology Reports

Volym

16

Issue

4

Dokumenttyp

Artikel i tidskrift

Förlag

Spandidos Publications

Ämne

  • Cancer and Oncology

Nyckelord

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

Status

Published

ISBN/ISSN/Övrigt

  • ISSN: 1791-2431