Abstract:Background
Better prognostic outcome is closely correlated with early detection of bladder cancer. Current non-invasive urianalysis relies on simultaneously testing multiple methylation markers to achieve relatively high accuracy. Therefore, we have developed an easy-to-use, convenient, and accurate single-target urine-based DNA methylation test for the malignancy.
Methods
By analyzing TCGA data, 344 candidate markers with 424 primer pairs and prob… Show more
“…Of all epigenetic modifications, DNA methylation has become the most intensely studied epigenetic modification in mammals. The covalent addition of a methyl group occurs generally in cytosine within cytosine‐guanine dinucleotide (CpG) islands 135,136 . In particular, hypermethylation that represses transcription of associated gene promoter regions leading to gene silencing has been most extensively studied because of its critical role in human carcinogenesis 137,138 .…”
Section: Urinary Liquid Biopsymentioning
confidence: 99%
“…The covalent addition of a methyl group occurs generally in cytosine within cytosineguanine dinucleotide (CpG) islands. 135,136 In particular, hypermethylation that represses transcription of associated gene promoter regions leading to gene silencing has been most extensively studied because of its critical role in human carcinogenesis. 137,138 Detected with the use of a polymerase chain reaction (PCR) on urinary cells, several DNA methylation genetic markers have been investigated increasingly in prostate cancer.…”
Prostate cancer remains the second-most common cancer diagnosed in men, despite the increasingly widespread use of serum prostate-specific antigen (PSA) screening. The controversial clinical implications and cost benefits of PSA screening have been highlighted due to its poor specificity, resulting in a high rate of overdiagnosis and underdiagnosis. Thus, the development of novel biomarkers for prostate cancer detection remains an intriguing challenge. Urine is emerging as a source for prostate cancer biomarker discovery.Currently, new urine biomarkers already outperform serum PSA in clinical diagnosis. Meanwhile, the advances in nanotechnology have provided a suite of diagnostic tools to study prostate cancer in more detail, sparking a new era of biomarker discoveries. In this review, we envision that future prostate cancer diagnosis will probably integrate multiplex nano-diagnostic approaches to detect novel urinary biomarkers. However, challenges remain in differentiating indolent from aggressive cancers to better inform treatment decisions, and clinical translation still needs to be overcome.This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
“…Of all epigenetic modifications, DNA methylation has become the most intensely studied epigenetic modification in mammals. The covalent addition of a methyl group occurs generally in cytosine within cytosine‐guanine dinucleotide (CpG) islands 135,136 . In particular, hypermethylation that represses transcription of associated gene promoter regions leading to gene silencing has been most extensively studied because of its critical role in human carcinogenesis 137,138 .…”
Section: Urinary Liquid Biopsymentioning
confidence: 99%
“…The covalent addition of a methyl group occurs generally in cytosine within cytosineguanine dinucleotide (CpG) islands. 135,136 In particular, hypermethylation that represses transcription of associated gene promoter regions leading to gene silencing has been most extensively studied because of its critical role in human carcinogenesis. 137,138 Detected with the use of a polymerase chain reaction (PCR) on urinary cells, several DNA methylation genetic markers have been investigated increasingly in prostate cancer.…”
Prostate cancer remains the second-most common cancer diagnosed in men, despite the increasingly widespread use of serum prostate-specific antigen (PSA) screening. The controversial clinical implications and cost benefits of PSA screening have been highlighted due to its poor specificity, resulting in a high rate of overdiagnosis and underdiagnosis. Thus, the development of novel biomarkers for prostate cancer detection remains an intriguing challenge. Urine is emerging as a source for prostate cancer biomarker discovery.Currently, new urine biomarkers already outperform serum PSA in clinical diagnosis. Meanwhile, the advances in nanotechnology have provided a suite of diagnostic tools to study prostate cancer in more detail, sparking a new era of biomarker discoveries. In this review, we envision that future prostate cancer diagnosis will probably integrate multiplex nano-diagnostic approaches to detect novel urinary biomarkers. However, challenges remain in differentiating indolent from aggressive cancers to better inform treatment decisions, and clinical translation still needs to be overcome.This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
“…Multiple gene sites in BC are hypermethylated, including Reprimo (RPRM), prostaglandin-endoperoxide synthase 2 (PTGS2), glutathione stransferase pi 1 (GSTP1) and APC regulator of the Wnt signalling pathway. By performing methylation-specific RT-qPCR on 477 urine samples (137 BCs, 202 control samples, 28 benign BCs and other related urinary cancer samples), Deng et al 60 found that the methylation level of DMRTA2 shows higher sensitivity in detecting early stages of BC (94.1% for T1, 96.4% for T2, 77.8% for T3 and 71.4% for T4). Moreover, the methylation level of DMRTA2 can also distinguish BC from other interfering urinary cancer and benign BC.…”
Urine‐based liquid biopsy has emerged as a non‐invasive and effective tool for early screening and diagnosis of bladder cancer. This review provides a comprehensive overview of the current urine‐based biomarkers and methods for the detection and monitoring of bladder cancer. We focus on biomarkers including tumour DNAs, proteins, microbiome, tumour RNAs, long non‐coding RNAs, transfer RNA‐derived fragments, messenger RNAs, microRNAs, circular RNAs, exosomes and extrachromosomal circular DNA.
“…Notably, however, Deng et al developed a single methylation biomarker model [ 74 ]. They used multiple validation steps involving TCGA data, BCa cell lines, and BCa patient cohorts to find the hypermethylation marker that provided the best diagnostic result; in the end, DMRTA2 achieved 82.9% SN and 92.5% SP, with an AUC of 0.93 in the diagnosis of BCa.…”
Section: Diagnostic Utility Of Biomarkers Assessed By Liquid Biopsymentioning
Early detection of primary bladder cancer (BCa) is vital, because stage and grade have been generally accepted not only as categorical but also as prognostic factors in patients with BCa. The widely accepted screening methods for BCa, cystoscopy and urine cytology, have unsatisfactory diagnostic accuracy, with high rates of false negatives, especially for flat-type BCa with cystoscopy and for low-risk disease with urine cytology. Currently, liquid biopsy has attracted much attention as being compensatory for that limited diagnostic power. In this review, we survey the literature on liquid biopsy for the detection of BCa, focusing on circulating tumor cells (CTCs), urinary cell-free DNA (ucfDNA), and urinary microRNA (umiRNA). In diagnostic terms, CTCs and umiRNA are determined by quantitative analysis, and ucfDNA relies on finding genetic and epigenetic changes. The ideal biomarkers should be highly sensitive in detecting BCa. Currently, CTCs produce an unfavorable result; however, umiRNA and ucfDNA, especially when analyzed using a panel of genes, produce promising results. However, given the small cohort size in most studies, no conclusions can yet be drawn about liquid biopsy’s immediate application to clinical practice. Further large studies to validate the diagnostic value of liquid biopsy for clinical use are mandatory.
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