A higher degree of expression of DNA methyl transferase 1 in cervical cancer is associated with poor survival outcome
Received 28 January 2017
Accepted for publication 31 March 2017
Published 8 June 2017 Volume 2017:9 Pages 413—420
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Professor Elie Al-Chaer
Chandrika J Piyathilake,1 Suguna Badiga,1 Samuel G Borak,2 Janaka Weragoda,1 Sejong Bae,3 Roland Matthews,4 Walter C Bell,2 Edward E Partridge5
1Department of Nutrition Sciences, 2Department of Pathology, 3Department of Medicine, The University of Alabama at Birmingham, Birmingham, AL, 4Department of Obstetrics and Gynecology, Morehouse School of Medicine, Atlanta, GA, 5Comprehensive Cancer Center, The University of Alabama at Birmingham, Birmingham, AL, USA
Background: Even though novel therapies based on aberrant DNA methylation could be of particular importance for the treatment of cervical cancer (CC) because the oncoproteins E6/E7 of high-risk human papillomaviruses, the causative agents for developing CC, have the capacity to bind and upregulate DNA methyltransferases (DNMTs), to our knowledge, no previous studies have evaluated the expression of this enzyme in CC in relation to survival outcomes. The purpose of the study was to evaluate the expression of DNMT1 in CC and its association with survival outcomes.
Methods: The study population consisted of 76 women treated for primary CC and followed up by the University of Alabama at Birmingham (UAB) cancer registry. The expression of DNMT1 was examined using immunohistochemistry, and the degree of expression of DNMT1 was expressed as a percentage of cells positive for DNMT1 and its intensity. Cox proportional hazards model was used to assess the relationship between the degree of expression of DNMT1 and overall survival after adjusting for relevant covariates.
Results: The expression of DNMT1 was significantly higher in CC cells compared to that in the normal cervical epithelium. A higher percentage of cells positive for DNMT1 and a higher intensity score for DNMT1 were significantly associated with poor survival outcome (hazard ratio [HR] =4.3, P=0.03 and HR =4.9, P=0.02, respectively).
Conclusion: Our findings suggested that the degree of expression of DNMT1 could be considered as a target in the epigenetic treatment of CC. Replication of our results in other study populations with CC could create the opportunity of using DNMT inhibitors to treat CC.
Keywords: DNMT1, cervical cancer, survival outcome
This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.Download Article [PDF] View Full Text [HTML][Machine readable]