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

Azzouzi, Meryem El; Ahanidi, Hajar El; Alaoui, Chaimae Hafidi; Chaoui, Imane; Benbacer, Laïla; Tetou, Mohamed; Hassan, Ilias; Bensaid, Mounia; Oukabli, Mohamed; Ameur, A.; Bouzidi, Abderrahmane Al; Mzibri, Mohammed El; Attaleb, Mohammed

doi:10.1016/j.cancergen.2021.12.001

Cited by 8 publications

(6 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These findings are in good agreement with already reported data on Moroccan patients [17]. Of interest, medium frequency of TERT (53%) and high frequency of TWIST1 (98%) promoters' methylation in BC were reported by Leão et al [14] and Yegin et al [16], respectively.…”

Section: Discussionsupporting

confidence: 92%

“…In this study, we have used MSP assay to assess the promoter methylation status of a panel of genes in both tumor biopsies and urine sediments DNA from Moroccan patients with bladder cancer. The interest was focused on, TWIST1, hTERT, NID2 and VIM genes for their implication in many cellular pathways and their widely reported data as highly methylated genes in bladder cancer [14][15][16][17].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Exploring urine sediments as a non-invasive method for DNA methylation detection in bladder cancer

et al. 2022

Self Cite

View full text Add to dashboard Cite

Background The main epigenetic event occurring during the bladder carcinogenesis process is DNA methylation, affecting genes involved in various metabolic pathways and cell regulation. The use of biological fluids such as urine sediments could be used as a non-invasive approach to enhance bladder cancer management. In this study, we aim to determine the promoter methylation status of a panel of genes in bladder cancer on tumor biopsies and urine sediments to evaluate the usefulness of urine samples as a non-invasive approach for methylation status assessment. Methods Using the methylation-specific PCR technique, we explored the promoter methylation status of hTERT, TWIST1, VIM and NID2 genes in 40 tumor biopsies and their paired urine samples from Moroccan bladder cancer patients. Results In this study, bladder tumors showed promoter hypermethylation frequency of individual genes as 90%, 85%, 62.5% and 72.5% in TWIST1, hTERT, NID2 and VIM genes, respectively. Interestingly, the specificity of methylation detection in urine samples was 100% and the sensitivity to detect hypermethylation of TWIST1, hTERT, NID2 and VIM genes reached 91.7%; 97.1%; 84% and 82.8%, respectively. Conclusions Our results clearly show that the assessment of promoter hypermethylation in urine samples is highly specific and has high sensitivity. Furthermore, urine sediments would be a useful approach to detect the DNA methylation status of genes and its potential association with bladder cancer development.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Exploring urine sediments as a non-invasive method for DNA methylation detection in bladder cancer

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…An improved urine DNA methylation panel of three biomarkers (PCDH17, POU4F2, and PENK) showed SN of 97% and SP of 87% in BC detection [ 98 ]. A study by El Azzouzi et al, showed a significant association between TWIST1 hypermethylation and BC recurrence and progression (66.67% and 80%), while hypermethylation of hTERT was found in 83.34% of recurrent and 80% of progression cases [ 99 ]. TWIST1 hypermethylation combined with SALL3 and CFTR showed an AUC of 0.86 and SN/SP of 90%/40% if combined with cytology [ 100 ].…”

Section: Epigenetic Modificationsmentioning

confidence: 99%

“…Guo et al used a 6-gene DNA methylation panel in the examination of urine from hematuria patients, which resulted in SN/SP of 89%/74% [ 110 ]. A recent study on BC patients in the Moroccan population showed VIM hypermethylation occurred in 67.14% of tumor samples, while hypermethylation in recurrent and progression cases accounted for 83.34% and 80%, respectively [ 99 ]. A study combining miR-663a with VIM proved effective in discriminating BC patients from inflammatory cases, with SN/SP of 80%/75% for miR-663a and SN/SP of 87%/86% for VIM [ 111 ].…”

Section: Epigenetic Modificationsmentioning

confidence: 99%

Biomarkers of Bladder Cancer: Cell-Free DNA, Epigenetic Modifications and Non-Coding RNAs

Harsanyi

Nováková

Bevizova

et al. 2022

IJMS

View full text Add to dashboard Cite

Bladder cancer (BC) is the 10th most frequent cancer in the world. The initial diagnosis and surveillance of BC require a combination of invasive and non-invasive methods, which are costly and suffer from several limitations. Cystoscopy with urine cytology and histological examination presents the standard diagnostic approach. Various biomarkers (e.g., proteins, genes, and RNAs) have been extensively studied in relation to BC. However, the new trend of liquid biopsy slowly proves to be almost equally effective. Cell-free DNA, non-coding RNA, and other subcellular structures are now being tested for the best predictive and diagnostic value. In this review, we focused on published gene mutations, especially in DNA fragments, but also epigenetic modifications, and non-coding RNA (ncRNA) molecules acquired by liquid biopsy. We performed an online search in PubMed/Medline, Scopus, and Web of Science databases using the terms “bladder cancer”, in combination with “markers” or “biomarkers” published until August 2022. If applicable, we set the sensitivity and specificity threshold to 80%. In the era of precision medicine, the development of complex laboratory techniques fuels the search and development of more sensitive and specific biomarkers for diagnosis, follow-up, and screening of BC. Future efforts will be focused on the validation of their sensitivity, specificity, predictive value, and their utility in everyday clinical practice.

show abstract

“…Epigenetics refers to changes in the expression of genes; though environmental factors can cause an organism's genes to be expressed differently, the genes will not be changed (9). Epigenetics processes include DNA methylation (10), genomic imprinting, maternal effects, gene silencing, dormant transposon activation, and RNA editing. Among these, DNA methylation refers to the covalent binding of a methyl group to the 5'carbon site of the CpG dinucleotide in the genome under the action of DNA methylating transferase (11,12).…”

Section: Introductionmentioning

confidence: 99%

Identification of adenylate cyclase 2 methylation in bladder cancer with implications for prognosis and immunosuppressive microenvironment

Yang

Gao

et al. 2022

Front. Oncol.

View full text Add to dashboard Cite

BackgroundThe incidence and mortality of bladder cancer (BCa) are increasing, while the existing diagnostic methods have limitations. Therefore, for early detection and response prediction, it is crucial to improve the prognosis and treatment strategies. However, with existing diagnostic methods, detecting BCa in the early stage is challenging. Hence, novel biomarkers are urgently needed to improve early diagnosis and treatment efficiency.MethodsThe gene expression profile and gene methylation profile dataset were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs), differentially methylated genes (DMGs), and methylation-regulated differentially expressed genes (MeDEGs) were gradually identified. A cancer genome map was obtained using online gene expression profile interaction analysis, and survival implications were produced using Kaplan-Meier survival analysis. GSEA was employed to predict the marker pathways where DEGs were significantly involved. The study used bisulfite PCR amplification combined with bisulfite amplicon sequencing (BSAS) to screen for methylation analysis of multiple candidate regions of the adenylate cyclase 2 (ADCY2) based on the sequence design of specific gene regions and CpG islands.ResultsIn this study, DEGs and DMGs with significantly up- or down-regulated expression were selected. The intersection method was used to screen the MeDEGs. The interaction network group in STRING was then visualized using Cytoscape, and the PPI network was constructed to identify the key genes. The key genes were then analyzed using functional enrichment. To compare the relationship between key genes and the prognosis of BCa patients, we further investigated ADCY2 and found that ADCY2 can be a potential clinical biomarker in BCa prognosis and immunotherapy response prediction. In human BCa 5637 and MGH1 cells, we developed and verified the effectiveness of ADCY2 primers using BSAS technology. The findings revealed that the expression of ADCY2 is highly regulated by the methylation of the promoter regions.ConclusionThis study revealed that increased expression of ADCY2 was significantly correlated with increased tumor heterogeneity, predicting worse survival and immunotherapy response in BCa patients.

show abstract

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

Cited by 8 publications

References 28 publications

Exploring urine sediments as a non-invasive method for DNA methylation detection in bladder cancer

Exploring urine sediments as a non-invasive method for DNA methylation detection in bladder cancer

Biomarkers of Bladder Cancer: Cell-Free DNA, Epigenetic Modifications and Non-Coding RNAs

Identification of adenylate cyclase 2 methylation in bladder cancer with implications for prognosis and immunosuppressive microenvironment

Contact Info

Product

Resources

About