Multi-institutional external validation of urinary TWIST1 and NID2 methylation as a diagnostic test for bladder cancer

Fantony, Joseph J.; Abern, Michael R.; Gopalakrishna, Ajay; Owusu, Richmond; Tay, Kae Jack; Lance, Raymond S.; Inman, Brant A.

doi:10.1016/j.urolonc.2015.04.014

Cited by 28 publications

(21 citation statements)

References 18 publications

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“…The bisulfite treatment of DNA is generally performed in conventional methylation assays, but this reaction can introduce various DNA strand breaks, resulting in single-stranded DNA with high fragmentation [16] and a DNA loss of around 90% [17]. After the bisulfite treatment of the DNA, these assays require a minimum of 10 copies of the target gene in the template DNA [18]. Thus, prior to bisulfite treatment, each template DNA would require at least 100 copies of the target gene if an expected 90% of the DNA is lost during the treatment [16].…”

Section: Discussionmentioning

confidence: 99%

Blood Free-Circulating DNA Testing of Methylated RUNX3 Is Useful for Diagnosing Early Gastric Cancer

Hideura

Suehiro

Nishikawa

et al. 2020

Cancers

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The main modalities for gastric cancer screening are limited to upper gastrointestinal endoscopy and contrast radiography. The former is invasive, and the latter has high false-negative rates. Thus, alternative diagnostic strategies are required. One solution may be a liquid biopsy. Methylated RUNX3 is a well-known biomarker of gastric cancer but it is very difficult to detect with conventional bisulfite-based methylation assays when only a small amount of serum is available. We developed the combined restriction digital PCR (CORD) assay, a new methylation assay allowing for the counting of as little as one copy of a methylated gene in a small sample of DNA without necessitating DNA bisulfite treatment. We evaluated the sensitivity and specificity of the serum DNA testing of methylated RUNX3 by the CORD assay for the detection of early gastric cancer using 50 patients with early gastric cancer and 61 control individuals. The CORD assay had a sensitivity of 50.0% and a specificity of 80.3% for early gastric cancer. Methylated RUNX3 copies were significantly associated with tumor size, massive submucosal invasion, and lymph-vascular invasion. After the treatment, the median number of methylated RUNX3 copies was significantly decreased. The CORD assay may provide an alternative screening strategy to detect even early-stage gastric cancer.

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Section: Discussionmentioning

confidence: 99%

Blood Free-Circulating DNA Testing of Methylated RUNX3 Is Useful for Diagnosing Early Gastric Cancer

Hideura

Suehiro

Nishikawa

et al. 2020

Cancers

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“…In other cancers, there were no promising methylation markers that could be used in clinics. Some of the gene candidates, such as NID2 or TWIST1 in urinary DNA, seemed to be promising markers, however, these studies are denied in prospective studies [86,98,100]. …”

Section: Discussionmentioning

confidence: 99%

“…Several other molecular markers have been developed; however, none of the markers were confirmed as promising markers. In this section, studies on methylation analyses using urinary DNA for the detection of bladder cancer are reviewed (Table 4 and Table S4) [76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98,99,100,101,102]. …”

Section: Use Of Bodily Fluids For Cancer Detectionmentioning

confidence: 99%

“…A higher sensitivity and feasible specificity were shown in both the training and validation sets (sensitivity; 88% and 94%, specificity; 94% and 91%, respectively), and, notably, a sensitivity of 80–89% was found for early-stage and low-grade cancer. This study, however, was later validated by two prospective studies that failed to replicate the excellent performance [98,100]. Recently, Dahmcke et al [102] conducted a prospective study for the detection of bladder cancer in a patient cohort of gross hematuria.…”

Section: Use Of Bodily Fluids For Cancer Detectionmentioning

confidence: 99%

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Analysis of DNA Methylation Status in Bodily Fluids for Early Detection of Cancer

Yokoi

Yamashita

Watanabe

2017

IJMS

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Epigenetic alterations by promoter DNA hypermethylation and gene silencing in cancer have been reported over the past few decades. DNA hypermethylation has great potential to serve as a screening marker, a prognostic marker, and a therapeutic surveillance marker in cancer clinics. Some bodily fluids, such as stool or urine, were obtainable without any invasion to the body. Thus, such bodily fluids were suitable samples for high throughput cancer surveillance. Analyzing the methylation status of bodily fluids around the cancer tissue may, additionally, lead to the early detection of cancer, because several genes in cancer tissues are reported to be cancer-specifically hypermethylated. Recently, several studies that analyzed the methylation status of DNA in bodily fluids were conducted, and some of the results have potential for future development and further clinical use. In fact, a stool DNA test was approved by the U.S. Food and Drug Administration (FDA) for the screening of colorectal cancer. Another promising methylation marker has been identified in various bodily fluids for several cancers. We reviewed studies that analyzed DNA methylation in bodily fluids as a less-invasive cancer screening.

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“…These hypermethylation events are not confounded by the need to cover multiple and often large regions for possible mutations (such as, for example, EGFR , APC , PIK3CA ). Hence there has been a growing interest in the application of assays for the detection of ctDNA by testing for specific methylated DNA biomarkers [17,18,19,20,21,22]. …”

Section: Introductionmentioning

confidence: 99%

Evaluation of Methylation Biomarkers for Detection of Circulating Tumor DNA and Application to Colorectal Cancer

Mitchell

Brown

et al. 2016

Genes

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Solid tumors shed DNA into circulation, and there is growing evidence that the detection of circulating tumor DNA (ctDNA) has broad clinical utility, including monitoring of disease, prognosis, response to chemotherapy and tracking tumor heterogeneity. The appearance of ctDNA in the circulating cell-free DNA (ccfDNA) isolated from plasma or serum is commonly detected by identifying tumor-specific features such as insertions, deletions, mutations and/or aberrant methylation. Methylation is a normal cell regulatory event, and since the majority of ccfDNA is derived from white blood cells (WBC), it is important that tumour-specific DNA methylation markers show rare to no methylation events in WBC DNA. We have used a novel approach for assessment of low levels of DNA methylation in WBC DNA. DNA methylation in 29 previously identified regions (residing in 17 genes) was analyzed in WBC DNA and eight differentially-methylated regions (DMRs) were taken through to testing in clinical samples using methylation specific PCR assays. DMRs residing in four genes, BCAT1, GRASP, IKZF1 and IRF4, exhibited low positivity, 3.5% to 7%, in the plasma of colonoscopy-confirmed healthy subjects, with the sensitivity for detection of ctDNA in colonoscopy-confirmed patients with colorectal cancer being 65%, 54.5%, 67.6% and 59% respectively.

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Multi-institutional external validation of urinary TWIST1 and NID2 methylation as a diagnostic test for bladder cancer

Cited by 28 publications

References 18 publications

Blood Free-Circulating DNA Testing of Methylated RUNX3 Is Useful for Diagnosing Early Gastric Cancer

Blood Free-Circulating DNA Testing of Methylated RUNX3 Is Useful for Diagnosing Early Gastric Cancer

Analysis of DNA Methylation Status in Bodily Fluids for Early Detection of Cancer

Evaluation of Methylation Biomarkers for Detection of Circulating Tumor DNA and Application to Colorectal Cancer

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