Promoter methylation analysis of CDH1 and p14ARF genes in patients with urothelial bladder cancer
Received 28 November 2017
Accepted for publication 1 April 2018
Published 19 July 2018 Volume 2018:11 Pages 4189—4196
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Cristina Weinberg
Peer reviewer comments 2
Editor who approved publication: Dr Jianmin Xu
Bayram Bayramov,1 Sezgin Gunes,1,2 Recep Buyukalpelli,2,3 Oğuz Aydın,4 Ralf Henkel5
1Medical Biology, Faculty of Medicine, Ondokuz Mayis University, Samsun, Turkey; 2Multidisciplinary Molecular Medicine, Health Sciences Institute, Ondokuz Mayis University, Samsun, Turkey; 3Urology, Faculty of Medicine, Ondokuz Mayis University, Samsun; 4Pathology, Faculty of Medicine, Ondokuz Mayis University, Samsun, Turkey; 5Department of Medical Bioscience, University of the Western Cape, Bellville, South Africa
Background/aim: Urothelial bladder cancer arises from the accumulation of multiple epigenetic and genetic changes. We aimed to investigate the specificity and sensitivity of gene-specific promoter methylation of CDH1 and p14ARF genes in the early diagnosis of bladder cancer and compare those with other diagnostic tests in our population.
Patients and methods: In the current study, 65 patients with urothelial bladder cancer and 35 controls without any history of cancer were recruited. Methylation profiles of CDH1 and p14ARF genes from tumor and urine samples were determined by methylation-specific polymerase chain reaction method.
Results: Methylation of CDH1 and p14ARF genes in tumor samples was 95.4% and 78.5%, respectively. The methylation frequencies were found to be 68.8% for CDH1 gene and 72.9% for p14ARF gene in urine samples. Sensitivities of CDH1, p14ARF and urine cytology were found to be 67.4%, 72.1% and 34.9%, respectively, while their specificities were 93.9%, 63.6% and 93.9%, respectively.
Conclusion: Aberrant promoter methylation of CDH1 and p14ARF genes can be used to detect urothelial bladder cancer. In low-grade tumors, when compared with urine cytology, combined methylation analysis of CDH1 and p14ARF genes may not increase the sensitivity to identify malignant cells in urine samples.
Keywords: biomarker, CDH1, urine cytology, urothelial bladder cancer, p14ARF, urine
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