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Kallikrein-related peptidase 6 (KLK6) expression in the progression of colon adenoma to carcinoma

  • Athina Vakrakou , Marina Devetzi , Georgia Papachristopoulou , Apostolos Malachias , Andreas Scorilas , Dimitris Xynopoulos and Maroulio Talieri EMAIL logo
Published/Copyright: August 6, 2014

Abstract

KLK6 is a secreted trypsin-like serine protease. KLK6 mRNA expression and its association with colon cancer (CC) progression was studied using quantitative real-time PCR. We examined the expression of KLK6 in 232 colon tissues (cancerous, non-cancerous, and adenomatous). We proved that KLK6 expression in CC behaves as a continuous variable, as its expression correlates significantly with increasing tumor stage (p=0.004) and histological grade (p=0.007). Interestingly, the expression of KLK6 in adenomas was significantly higher than that in the cancerous or non-cancerous tissues examined (p<0.001). Cox proportional hazard regression model using univariate analysis revealed that positive KLK6 expression is a significant factor for disease-free survival (DFS) (p=0.017) and overall survival (OS) (p=0.002) of patients. Kaplan-Meier survival curves demonstrated that KLK6-negative expression is significantly associated with longer DFS (p=0.009) and OS (p=0.001). ROC analysis showed that KLK6 expression has significant discriminatory power in distinguishing cancerous from non-cancerous colon tissues (p<0.001), or cancerous from adenoma tissues (p=0.001), or adenoma from non-cancerous colon tissues (p<0.001). Additionally, strong KLK6 immunostaining was seen in the cancer cells of selected CC sections, as well as in glandular cells and inflammatory cells of adenomas. In conclusion, KLK6 may represent a potential unfavorable prognostic biomarker for CC.


Corresponding author: Maroulio Talieri, Department of Cellular Physiology, G. Papanicolaou Research Center of Oncology, Saint Savvas Oncologic Anticancer Hospital, 171 Alexandras Avenue, GR-11522 Athens, Greece, e-mail: ;
aThese authors contributed equally to this work.

Acknowledgments

The authors want to thank Prof. E.P. Diamandis from the Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Canada, for providing the KLK6 antibody.

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Received: 2014-3-15
Accepted: 2014-7-9
Published Online: 2014-8-6
Published in Print: 2014-9-1

©2014 by De Gruyter

Articles in the same Issue

  1. Frontmatter
  2. Guest Editorial
  3. Highlight: The 5th International Symposium on Kallikreins and Kallikrein-Related Peptidases
  4. KLKs and their hormone-like signaling actions: a new life for the PSA-KLK family
  5. Putative kallikrein substrates and their (patho)biological functions
  6. Netherton syndrome: defective kallikrein inhibition in the skin leads to skin inflammation and allergy
  7. Sweetened kallikrein-related peptidases (KLKs): glycan trees as potential regulators of activation and activity
  8. Activation of membrane-bound proteins and receptor systems: a link between tissue kallikrein and the KLK-related peptidases
  9. Kallikreins are involved in an miRNA network that contributes to prostate cancer progression
  10. Evolution of Klk4 and enamel maturation in eutherians
  11. Growth and survival of lung cancer cells: regulation by kallikrein-related peptidase 6 via activation of proteinase-activated receptor 2 and the epidermal growth factor receptor
  12. CrataBL, a lectin and Factor Xa inhibitor, plays a role in blood coagulation and impairs thrombus formation
  13. Mining for single nucleotide variants (SNVs) at the kallikrein locus with predicted functional consequences
  14. Low mRNA expression levels of kallikrein-related peptidase 4 (KLK4) predict short-term relapse in patients with laryngeal squamous cell carcinoma
  15. Differential expression of multiple kallikreins in a viral model of multiple sclerosis points to unique roles in the innate and adaptive immune response
  16. Kallikrein-related peptidase 7 (KLK7) is a proliferative factor that is aberrantly expressed in human colon cancer
  17. Prognostic significance of human tissue kallikrein-related peptidases 6 and 10 in gastric cancer
  18. Loss of miR-378 in prostate cancer, a common regulator of KLK2 and KLK4, correlates with aggressive disease phenotype and predicts the short-term relapse of the patients
  19. Kallikrein-related peptidase 6 (KLK6) expression in the progression of colon adenoma to carcinoma
  20. Development of monoclonal antibodies to human kallikrein-related peptidase 6 (KLK6) and their use in an immunofluorometric assay for free KLK6
  21. Analysis of androgen and anti-androgen regulation of KLK-related peptidase 2, 3, and 4 alternative transcripts in prostate cancer
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