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

Werle, Bernd ; Schanzenbaecher, Ulrike ; Lah, Tamara Turensek ; Ebert, Eileen ; Juelke, Britta ; Ebert, Werner ; Fiehn, Werner ; Kayser, Klaus ; Spiess, Eberhard and Abrahamson, Magnus LU , et al. (2006) In Oncology Reports 16(4). p.647-655
Abstract
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... (More)
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. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
cancer, non-small cell lung, cathepsin, cysteine protease, stefin, cystatin, prognosis
in
Oncology Reports
volume
16
issue
4
pages
647 - 655
publisher
D.A. Spandidos
external identifiers
  • wos:000240879000001
  • scopus:33845286615
ISSN
1791-2431
language
English
LU publication?
yes
id
bbe38ead-be38-4e9b-bba3-679c5a6477b7 (old id 389447)
alternative location
http://147.52.72.117/OR/2006/volume16/number4/647.pdf
date added to LUP
2016-04-01 15:25:40
date last changed
2020-08-26 03:00:15
@article{bbe38ead-be38-4e9b-bba3-679c5a6477b7,
  abstract     = {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 &lt; 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 &lt; 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 &lt; 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 &lt; 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.},
  author       = {Werle, Bernd and Schanzenbaecher, Ulrike and Lah, Tamara Turensek and Ebert, Eileen and Juelke, Britta and Ebert, Werner and Fiehn, Werner and Kayser, Klaus and Spiess, Eberhard and Abrahamson, Magnus and Kos, Janko},
  issn         = {1791-2431},
  language     = {eng},
  number       = {4},
  pages        = {647--655},
  publisher    = {D.A. Spandidos},
  series       = {Oncology Reports},
  title        = {Cystatins in non-small cell lung cancer: Tissue levels, localization and relation to prognosis},
  url          = {http://147.52.72.117/OR/2006/volume16/number4/647.pdf},
  volume       = {16},
  year         = {2006},
}