Evaluation of DNA methylation in promoter regions of hTERT, TWIST1, VIM and NID2 genes in Moroccan bladder cancer patients

• Published in: Cancer genetics Vol. 260-261; pp. 41 - 45
• Main Authors: El Azzouzi, Meryem, El Ahanidi, Hajar, Hafidi Alaoui, Chaimae, Chaoui, Imane, Benbacer, Laila, Tetou, Mohamed, Hassan, Ilias, Bensaid, Mounia, Oukabli, Mohamed, Ameur, Ahmed, Al Bouzidi, Abderrahmane, El Mzibri, Mohammed, Attaleb, Mohammed
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-01-2022
• Subjects: Aged; Aged, 80 and over; Biomarkers, Tumor - genetics; Bladder cancer; Calcium-Binding Proteins - genetics; Cell Adhesion Molecules - genetics; DNA Methylation; Epigenetics; Female; Genetic Association Studies; Humans; Male; Methylation specific PCR; Middle Aged; Morocco; Neoplasm Grading; Neoplasm Staging; Nuclear Proteins - genetics; Promoter Regions, Genetic; Recurrence; Telomerase - genetics; Twist-Related Protein 1 - genetics; Urinary Bladder Neoplasms - genetics; Urinary Bladder Neoplasms - pathology; Vimentin - genetics; Morocco; Methylation specific PCR; Epigenetics; DNA methylation; Recurrence; Bladder cancer
• ISSN: 2210-7762; 2210-7770
• DOI: 10.1016/j.cancergen.2021.12.001

•Hypermethylation of promoter regions of hTERT, TWIST1, VIM and NID2 is a frequent epigenetic event in bladder cancer.•TWIST1 hypermethylation can be considered as a prognostic biomarker for bladder cancer recurrence.•Methylation mechanism abnormalities in cancer cells could be a promising therapeutic target to prevent bladder cancer progression and metastasis.
Promoter hypermethylation have been reported to play a key role in bladder cancer development and progression. The aim of this study is to evaluate the methylation status of hTERT, TWIST1, VIM and NID2 genes in bladder cancer. The methylation status was evaluated using the Methylation-Specific PCR (MSP) approach on 70 tumour biopsies from Moroccan bladder cancer patients. Overall, methylation frequencies of hTERT, TWIST1, VIM and NID2 genes, were 90%, 85.71%, 67.14% and 67.14%, respectively. Hypermethylation of all studied genes was found in all pathological grades and stages of bladder cancer. Nevertheless, statistical analysis showed no significant association between promoter methylation of hTERT, TWIST1, VIM and NID2 genes and tumours stage/grade (p value >0.05). Moreover, we have investigated the association between the methylation pattern of selected genes and the treatment outcome in a sub-group of non-muscle-invasive bladder cancer cases (52/70). Hypermethylation of hTERT, TWIST1, VIM and NID2 was detected in 83.34%; 66.67%; 83.34% and 58.34% of recurrent cases, respectively, and in 80%; 80%; 80% and 60% of progressive cases, respectively. Statistical analysis highlighted a significant association between TWIST1 hypermethylation and tumour recurrence (p = 0.041<0.05).
Our results indicate that hypermethylation of hTERT, TWIST1, VIM and NID2 genes is a frequent epigenetic event in bladder cancer and could be a promising therapeutic target to prevent bladder cancer progression and metastasis.