Identification of Prognostic Biomarkers for Bladder Cancer Based on DNA Methylation Profile

Zhang, Shumei; Zhang, Jingyu; Zhang, Qichao; Liang, Yingjian; Du, Ye; Wang, Guohua

doi:10.3389/fcell.2021.817086

Cited by 10 publications

(7 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…First, our results need external validation in a larger cohort multicenter study. Second, our analysis included only hypermethylation study with lack of other analyses that can optimize the diagnostic capacity as mutation analysis [ 28 ]. Third, lack of further study of evaluated genes DNA methylation on future tumor recurrence and/or progression is a considerable limitation.…”

Section: Discussionmentioning

confidence: 99%

Novel urine-based DNA methylation biomarkers for urothelial bladder carcinoma detection in patients with hematuria

Abol-Elnazer,

Awadalla,

Ahmed

et al. 2023

Arab Journal of Urology

View full text Add to dashboard Cite

Background Urothelial bladder carcinoma (UBC) is usually detected during work-up for hematuria. Cystoscopy and/or contrast-enhanced imaging are the gold standard tools for UBC diagnosis, despite limited by being invasive, expensive and low yield in small flat tumors. Objectives To assess the diagnostic performance of urine-based DNA methylation of six genes (GATA4, P16, P14, APC, CDH1 and CD99) for UBC detection in patients with hematuria. Patients and methods Voided urine was collected from consecutive patients presented with hematuria for urine cytology and DNA methylation assay of the assigned genes using methylation-specific Polymerase Chain Reaction (PCR). Further assessment by office cystoscopy and imaging with subsequent inpatient cystoscopic biopsy for positive findings was done. The diagnostic characteristics of DNA methylation and urine cytology were assessed based on its capability to predict UBC. Results We included 246 patients in the study with identified macroscopic hematuria in 204 (82.9%) patients. Positive cytology was found in 78 (31.7%) patients. DNA methylation of GATA4, P16, P14, APC, CDH1 and CD99 genes was identified in 127 (51.6%), 52 (21.1%), 117 (47.6%), 106 (43.1%), 90 (36.6%) and 71 (28.9%) patients, respectively. The sensitivity of the assigned genes for UBC detection ranges from 35% (95%CI: 31–39) to 83% (95%CI: 79–87). Optimal specificity (SP) (100%) was noted for P16, APC and CDH1 genes. While for the other genes (GATA4, P14 and CD99), the SP was 95% (95%CI: 92–98), 96% (95%CI: 92–99) and 97% (95%CI: 93–99), respectively. On multivariate logistic regression analysis, all genes exclusively demonstrated independent prediction of UBC. On receiver operator characteristic (ROC) analysis, all tested genes methylation showed superior area under the curve (AUC) when compared to urine cytology. Conclusions We have developed a novel urine-based DNA methylation assay for detection of UBC in patients with hematuria with superior diagnostic performance and independent predictive capacity over urine cytology.

show abstract

Section: Discussionmentioning

confidence: 99%

Novel urine-based DNA methylation biomarkers for urothelial bladder carcinoma detection in patients with hematuria

Abol-Elnazer,

Awadalla,

Ahmed

et al. 2023

Arab Journal of Urology

View full text Add to dashboard Cite

show abstract

“…Epigenetic modifications include histone modification, DNA methylation, and effects of ncRNA. Histone modification is not thoroughly studied, but DNA methylation is an important epigenetic modification, which plays an important role in regulating gene expression at the transcriptional level [ 97 ]. In tumor research, it has been found that the change in DNA methylation leads to the abnormality of gene structure and function, which can provide an early warning for tumorigenesis.…”

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

“…DNA methylation is a significant epigenetic alteration that has a significant impact on the transcriptional regulation of gene expression. In studies on tumors, it has been discovered that altering DNA methylation results in abnormalities in gene structure and function, which can serve as an early indicator of the development of tumors 20 . Additionally, many studies have been undertaken to understand the epigenetic mechanism behind cancer progression and resistance 21 , 22 .…”

Section: Introductionmentioning

confidence: 99%

Identification and validation of prognostic signature genes of bladder cancer by integrating methylation and transcriptomic analysis

Chatterjee,

Mou,

Sultana

et al. 2024

Sci Rep

View full text Add to dashboard Cite

Being a frequent malignant tumor of the genitourinary system, Bladder Urothelial Carcinoma (BLCA) has a poor prognosis. This study focused on identifying and validating prognostic biomarkers utilizing methylation, transcriptomics, and clinical data from The Cancer Genome Atlas Bladder Urothelial Carcinoma (TCGA BLCA) cohort. The impact of altered differentially methylated hallmark pathway genes was subjected to clustering analysis to observe changes in the transcriptional landscape on BLCA patients and identify two subtypes of patients from the TCGA BLCA population where Subtype 2 was associated with the worst prognosis with a p-value of 0.00032. Differential expression and enrichment analysis showed that subtype 2 was enriched in immune-responsive and cancer-progressive pathways, whereas subtype 1 was enriched in biosynthetic pathways. Following, regression and network analyses revealed Epidermal Growth Factor Receptor (EGFR), Fos-related antigen 1 (FOSL1), Nuclear Factor Erythroid 2 (NFE2), ADP-ribosylation factor-like protein 4D (ARL4D), SH3 domain containing ring finger 2 (SH3RF2), and Cadherin 3 (CDH3) genes to be the most significant prognostic gene markers. These genes were used to construct a risk model that separated the BLCA patients into high and low-risk groups. The risk model was also validated in an external dataset by performing survival analysis between high and low-risk groups with a p-value < 0.001 and the result showed the high group was significantly associated with poor prognosis compared to the low group. Single-cell analyses revealed the elevated level of these genes in the tumor microenvironment and associated with immune response. High-grade patients also tend to have a high expression of these genes compared to low-grade patients. In conclusion, this research developed a six-gene signature that is pertinent to the prediction of overall survival (OS) and might contribute to the advancement of precision medicine in the management of bladder cancer.

show abstract

Identification of Prognostic Biomarkers for Bladder Cancer Based on DNA Methylation Profile

Cited by 10 publications

References 65 publications

Novel urine-based DNA methylation biomarkers for urothelial bladder carcinoma detection in patients with hematuria

Novel urine-based DNA methylation biomarkers for urothelial bladder carcinoma detection in patients with hematuria

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

Identification and validation of prognostic signature genes of bladder cancer by integrating methylation and transcriptomic analysis

Contact Info

Product

Resources

About