Promoter methylation analysis of CDH1 and p14ARF genes in patients with urothelial bladder cancer

被引:7
作者
Bayramov, Bayram [1 ]
Gunes, Sezgin [1 ,2 ]
Buyukalpelli, Recep [2 ,3 ]
Aydin, Oguz [4 ]
Henkel, Ralf [5 ]
机构
[1] Ondokuz Mayis Univ, Fac Med, Med Biol, TR-55139 Samsun, Turkey
[2] Ondokuz Mayis Univ, Hlth Sci Inst, Multidisciplinary Mol Med, Samsun, Turkey
[3] Ondokuz Mayis Univ, Fac Med, Urol, Samsun, Turkey
[4] Ondokuz Mayis Univ, Fac Med, Pathol, Samsun, Turkey
[5] Univ Western Cape, Dept Med Biosci, Bellville, South Africa
关键词
biomarker; CDH1; urine cytology; urothelial bladder cancer; p14ARF; urine; E-CADHERIN GENE; DNA METHYLATION; MULTIPLE GENES; TUMOR-TISSUES; RASSF1A GENES; VOIDED URINE; HYPERMETHYLATION; BIOMARKERS; P16; ARF;
D O I
10.2147/OTT.S158259
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
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.
引用
收藏
页码:4189 / 4196
页数:8
相关论文
共 40 条
[1]  
[Anonymous], 2016, BIOL TRACE ELEM RES
[2]   Methylation of the E-cadherin gene in bladder neoplasia and in normal urothelial epithelium from elderly individuals [J].
Bornman, DM ;
Mathew, S ;
Alsruhe, J ;
Herman, JG ;
Gabrielson, E .
AMERICAN JOURNAL OF PATHOLOGY, 2001, 159 (03) :831-835
[3]   Gender- and smoking-related bladder cancer risk [J].
Castelao, JE ;
Yuan, JM ;
Skipper, PL ;
Tannenbaum, SR ;
Gago-Dominguez, M ;
Crowder, JS ;
Ross, RK ;
Yu, MC .
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2001, 93 (07) :538-545
[4]  
Chan MWY, 2002, CLIN CANCER RES, V8, P464
[5]   Distinct DNA methylation epigenotypes in bladder cancer from different Chinese sub-populations and its implication in cancer detection using voided urine [J].
Chen, Pi-Che ;
Tsai, Ming-Hsuan ;
Yip, Sidney K. H. ;
Jou, Yeong-Chin ;
Ng, Chi-Fai ;
Chen, Yanning ;
Wang, Xiaoling ;
Huang, Wei ;
Tung, Chun-Liang ;
Chen, Gary C. W. ;
Huang, Martin M. S. ;
Tong, Joanna H. M. ;
Song, Eing-Ju ;
Chang, De-Ching ;
Hsu, Cheng-Da ;
To, Ka-Fai ;
Shen, Cheng-Huang ;
Chan, Michael W. Y. .
BMC MEDICAL GENOMICS, 2011, 4
[6]   A Prospective Blinded Evaluation of Urine-DNA Testing for Detection of Urothelial Bladder Carcinoma in Patients with Gross Hematuria [J].
Dahmcke, Christina M. ;
Steven, Kenneth E. ;
Larsen, Louise K. ;
Poulsen, Asger L. ;
Abdul-Al, Ahmad ;
Dahl, Christina ;
Guldberg, Per .
EUROPEAN UROLOGY, 2016, 70 (06) :916-919
[7]  
Di Pierro GB, 2012, CURR GENOMICS, V13, P395, DOI 10.2174/138920212801619232
[8]   Prevalence of aberrant methylation of p14ARF over p16INK4a in some human primary tumors [J].
Dominguez, G ;
Silva, J ;
Garcia, JM ;
Silva, JM ;
Rodriguez, R ;
Muñoz, C ;
Chacón, I ;
Sanchez, R ;
Carballido, J ;
Colás, A ;
España, P ;
Bonilla, F .
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS, 2003, 530 (1-2) :9-17
[9]   Detection of bladder cancer in urine by a tumor suppressor gene hypermethylation panel [J].
Dulaimi, E ;
Uzzo, RG ;
Greenberg, RE ;
Al-Saleem, T ;
Cairns, P .
CLINICAL CANCER RESEARCH, 2004, 10 (06) :1887-1893
[10]   Epigenetics and aging: the targets and the marks [J].
Fraga, Mario F. ;
Esteller, Manel .
TRENDS IN GENETICS, 2007, 23 (08) :413-418