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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Greaves, Ronda / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter


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Volume 57, Issue 8

Issues

Uncovering the clinical impact of kallikrein-related peptidase 5 (KLK5) mRNA expression in the colorectal adenoma-carcinoma sequence

Georgia Papachristopoulou
  • Department of Pathology, “Saint Savvas” Cancer Hospital of Athens, Athens, Greece
  • Department of Biochemistry and Molecular Biology, National and Kapodistrian University of Athens, Athens, Greece
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Apostolos Malachias / Marina Devetzi
  • Department of Cellular Physiology, G. Papanicolaou Research Center of Oncology, “Saint Savvas” Cancer Hospital of Athens, Athens, Greece
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Evdoxia KamouzaORCID iD: https://orcid.org/0000-0003-4453-930X / Andreas ScorilasORCID iD: https://orcid.org/0000-0003-2427-4949 / Dimitris Xynopoulos / Maroulio Talieri
  • Corresponding author
  • Department of Cellular Physiology, G. Papanicolaou Research Center of Oncology, “Saint Savvas” Cancer Hospital of Athens, Athens, Greece
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2019-02-13 | DOI: https://doi.org/10.1515/cclm-2018-1010

Abstract

Background

Kallikrein-related peptidases (KLKs) are a subgroup of serine proteases located on chromosome 19q13.3. Most KLKs have been extensively studied as potential biomarkers for several carcinomas and other diseases. KLK5 was originally identified from a keratinocyte library, and its enzyme was purified from the stratum corneum of human skin. KLK5 was shown to be differentially expressed in a variety of endocrine tumors, although it is not as yet examined widely in colorectal cancer (CRC).

Methods

In this study, we quantitatively assessed the mRNA expression status of KLK5 in 197 colorectal tissues from 133 patients (70 cancerous and their paired normal colonic mucosa for 64 of them, as well as 63 colorectal adenomas) by quantitative real-time PCR (qPCR) using TaqMan probes. Statistical analysis evaluated the results.

Results

It was shown that KLK5 expression is reduced following the histologically non-cancerous-adenoma sequence (p<0.001), whereas it is increased during the sequence adenoma-carcinoma (p<0.001). Furthermore, KLK5 positive expression is associated with positive nodal status (p=0.022), advanced tumor stage (p=0.038) and high histological grade (p=0.033). Cox univariate analysis revealed that KLK5 positive expression is associated with disease-free survival (DFS) (p=0.028) and overall survival (OS) of patients (p=0.048). Kaplan-Meyer survival models showed that patients with positive KLK5 expression have lower DFS (p=0.009) and OS (p=0.019). Receiver operating characteristic (ROC) analysis demonstrated for first time that KLK5 expression had significant discriminatory values between cancer and adenoma tissues (area under the curve [AUC] 0.77; 95% confidence interval [CI]=0.69–0.85, p=0.03).

Conclusions

KLK5 mRNA expression may be useful for the differentiation of CRC from colorectal adenoma and represents a potential unfavorable prognostic biomarker for CRC.

Keywords: colon cancer; gastrointestinal cancer; molecular tumor markers; prognosis; prognostic biomarkers; quantitative real-time PCR (qPCR)

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About the article

Corresponding author: Dr. Maroulio Talieri, Department of Cellular Physiology, G. Papanicolaou Research Center of Oncology, “Saint Savvas” Cancer Hospital of Athens, 171 Alexandras Avenue, 11522 Athens, Greece, Phone: +30 2106424163, Fax: +30 2106424163, E-mail: litsa.talieri@yahoo.com

aDeceased


Received: 2018-09-13

Accepted: 2019-01-08

Published Online: 2019-02-13

Published in Print: 2019-07-26


Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.


Citation Information: Clinical Chemistry and Laboratory Medicine (CCLM), Volume 57, Issue 8, Pages 1251–1260, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/cclm-2018-1010.

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