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Cathepsin K associates with lymph node metastasis and poor prognosis in oral squamous cell carcinoma

BACKGROUND: Lymph node metastasis (LNM) is a major determinant of prognosis and treatment planning of oral squamous cell carcinoma (OSCC). Cysteine cathepsins constitute a family of proteolytic enzymes with known role in the degradation of the extracellular matrix. Involvement in pathological proces...

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Autores principales: Leusink, Frank K., Koudounarakis, Eleftherios, Frank, Michael H., Koole, Ronald, van Diest, Paul J., Willems, Stefan M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5885370/
https://www.ncbi.nlm.nih.gov/pubmed/29618339
http://dx.doi.org/10.1186/s12885-018-4315-8
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author Leusink, Frank K.
Koudounarakis, Eleftherios
Frank, Michael H.
Koole, Ronald
van Diest, Paul J.
Willems, Stefan M.
author_facet Leusink, Frank K.
Koudounarakis, Eleftherios
Frank, Michael H.
Koole, Ronald
van Diest, Paul J.
Willems, Stefan M.
author_sort Leusink, Frank K.
collection PubMed
description BACKGROUND: Lymph node metastasis (LNM) is a major determinant of prognosis and treatment planning of oral squamous cell carcinoma (OSCC). Cysteine cathepsins constitute a family of proteolytic enzymes with known role in the degradation of the extracellular matrix. Involvement in pathological processes, such as inflammation and cancer progression, has been proved. The aim of the study was to discover the clinicopathological and prognostic implications of cathepsin K (CTSK) expression in oral squamous cell carcinoma. METHODS: Eighty-three patients with primary OSCC, treated surgically between 1996 and 2000, were included. Gene expression data were acquired from a previously reported study. Human papilloma virus (HPV) status was previously determined by an algorithm for HPV-16. CTSK Protein expression was semi-quantitatively determined by immunohistochemistry in tumor and stromal cells. Expression data were correlated with various clinicopathological variables. RESULTS: Elevated gene and protein expression of CTSK were strongly associated to LNM and perineural invasion (p < 0.01). Logistic regression analysis highlighted increased CTSK protein expression in tumor cells as the most significant independent factor of lymphatic metastasis (OR = 7.65, CI:2.31–23.31, p = 0.001). Survival analysis demonstrated CTSK protein expression in both stromal and tumor cells as significant indicators of poor 5-year disease specific survival (HR = 2.40, CI:1.05–5.50, p = 0.038 for stromal cells; HR = 2.79, CI:1.02–7.64, p = 0.045 for tumor cells). CONCLUSION: Upregulation of CTSK seems to be associated with high incidence of lymphatic spread and poor survival in OSCC. CTSK could therefore serve as a predictive biomarker for OSCC. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-018-4315-8) contains supplementary material, which is available to authorized users.
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spelling pubmed-58853702018-04-09 Cathepsin K associates with lymph node metastasis and poor prognosis in oral squamous cell carcinoma Leusink, Frank K. Koudounarakis, Eleftherios Frank, Michael H. Koole, Ronald van Diest, Paul J. Willems, Stefan M. BMC Cancer Research Article BACKGROUND: Lymph node metastasis (LNM) is a major determinant of prognosis and treatment planning of oral squamous cell carcinoma (OSCC). Cysteine cathepsins constitute a family of proteolytic enzymes with known role in the degradation of the extracellular matrix. Involvement in pathological processes, such as inflammation and cancer progression, has been proved. The aim of the study was to discover the clinicopathological and prognostic implications of cathepsin K (CTSK) expression in oral squamous cell carcinoma. METHODS: Eighty-three patients with primary OSCC, treated surgically between 1996 and 2000, were included. Gene expression data were acquired from a previously reported study. Human papilloma virus (HPV) status was previously determined by an algorithm for HPV-16. CTSK Protein expression was semi-quantitatively determined by immunohistochemistry in tumor and stromal cells. Expression data were correlated with various clinicopathological variables. RESULTS: Elevated gene and protein expression of CTSK were strongly associated to LNM and perineural invasion (p < 0.01). Logistic regression analysis highlighted increased CTSK protein expression in tumor cells as the most significant independent factor of lymphatic metastasis (OR = 7.65, CI:2.31–23.31, p = 0.001). Survival analysis demonstrated CTSK protein expression in both stromal and tumor cells as significant indicators of poor 5-year disease specific survival (HR = 2.40, CI:1.05–5.50, p = 0.038 for stromal cells; HR = 2.79, CI:1.02–7.64, p = 0.045 for tumor cells). CONCLUSION: Upregulation of CTSK seems to be associated with high incidence of lymphatic spread and poor survival in OSCC. CTSK could therefore serve as a predictive biomarker for OSCC. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-018-4315-8) contains supplementary material, which is available to authorized users. BioMed Central 2018-04-05 /pmc/articles/PMC5885370/ /pubmed/29618339 http://dx.doi.org/10.1186/s12885-018-4315-8 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Leusink, Frank K.
Koudounarakis, Eleftherios
Frank, Michael H.
Koole, Ronald
van Diest, Paul J.
Willems, Stefan M.
Cathepsin K associates with lymph node metastasis and poor prognosis in oral squamous cell carcinoma
title Cathepsin K associates with lymph node metastasis and poor prognosis in oral squamous cell carcinoma
title_full Cathepsin K associates with lymph node metastasis and poor prognosis in oral squamous cell carcinoma
title_fullStr Cathepsin K associates with lymph node metastasis and poor prognosis in oral squamous cell carcinoma
title_full_unstemmed Cathepsin K associates with lymph node metastasis and poor prognosis in oral squamous cell carcinoma
title_short Cathepsin K associates with lymph node metastasis and poor prognosis in oral squamous cell carcinoma
title_sort cathepsin k associates with lymph node metastasis and poor prognosis in oral squamous cell carcinoma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5885370/
https://www.ncbi.nlm.nih.gov/pubmed/29618339
http://dx.doi.org/10.1186/s12885-018-4315-8
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