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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

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Volume 395, Issue 9


Low mRNA expression levels of kallikrein-related peptidase 4 (KLK4) predict short-term relapse in patients with laryngeal squamous cell carcinoma

Emmanouela Foteinou
  • Department of Biochemistry and Molecular Biology, University of Athens, GR-15701 Athens, Greece
  • Other articles by this author:
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/ Christos K. Kontos
  • Department of Biochemistry and Molecular Biology, University of Athens, GR-15701 Athens, Greece
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/ Aris I. Giotakis
  • First Ear, Nose and Throat Clinics, Athens General Hospital ‘Hippokration’, University of Athens, GR-11527 Athens, Greece
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/ Andreas Scorilas
  • Corresponding author
  • Department of Biochemistry and Molecular Biology, University of Athens, GR-15701 Athens, Greece
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Published Online: 2014-04-11 | DOI: https://doi.org/10.1515/hsz-2014-0139


Several members of the family of tissue kallikrein and kallikrein-related peptidases have been suggested as promising tumor biomarkers with important prognostic significance. However, only one (KLK11) has already been studied in laryngeal squamous cell carcinoma (LSCC) as a potential biomarker for LSCC diagnosis and/or prognosis. Our study investigated the prognostic value of kallikrein-related peptidase-4 (KLK4) mRNA expression as a molecular tissue biomarker in LSCC. For this purpose, KLK4 mRNA expression analysis was performed in 116 cancerous and 74 paired non-cancerous laryngeal tissue specimens obtained from patients that had undergone surgical treatment for primary LSCC. A remarkable downregulation of KLK4 mRNA expression was discovered in laryngeal tumors, compared to non-cancerous laryngeal tissue specimens. KLK4 mRNA expression was also shown to distinguish LSCC from non-cancerous laryngeal tissues. Furthermore, low KLK4 mRNA expression was shown to predict poor disease-free survival, independently of the histological grade and size of the malignant tumor as well as patient TNM stage. According to Kaplan-Meier survival analysis, low KLK4 mRNA expression predicts short-term relapse even among patients with well-differentiated tumors or those at an early TNM stage. Thus, KLK4 mRNA positivity could be regarded as a novel independent indicator of favorable prognosis for the disease-free survival of LSCC patients.

Keywords: head and neck cancer; kallikreins; molecular tumor biomarkers; oral cancer; prognostic biomarkers; quantitative real-time PCR


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About the article

Corresponding author: Andreas Scorilas, Department of Biochemistry and Molecular Biology, University of Athens, GR-15701 Athens, Greece, e-mail:

Received: 2014-02-15

Accepted: 2014-04-08

Published Online: 2014-04-11

Published in Print: 2014-09-01

Citation Information: Biological Chemistry, Volume 395, Issue 9, Pages 1051–1062, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/hsz-2014-0139.

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