Detection of urothelial carcinoma, upper tract urothelial carcinoma, bladder carcinoma, and urothelial carcinoma with gross hematuria using selected urine-DNA methylation biomarkers: A prospective, single-center study

Guo, Run-Qi; Xiong, Gengyan; Yang, Kaiwei; Zhang, Lei; He, Shiming; Gong, Yanqing; He, Qun; Li, Xueying; Wang, Zicheng; Bao, Zhen-Qing; Li, Xuesong; Zhang, Kai; Zhou, Liqun

doi:10.1016/j.urolonc.2018.04.001

Cited by 41 publications

(30 citation statements)

References 27 publications

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“…With the singly use of ONECUT2 methylation test in this cutoff value, genetic abnormalities in 89.1% (57/64) urine of UTUC+ patients and 5.8% (5/86) of UTUC-group were detected resulting in a sensitivity of 89.1% (57/64), and a speci city of 94.2% (81/86) ( Table 3). This performance of the ONECUT2 methylation test was better than the one reported previously (sensitivity of 82% and speci city of 62% with a panel of VIM, RASSF1A, GDF15, and TMEFF2 methylation in UTUC group) [18] .…”

Section: Univariate Logistic Regression Of Signi Cant Featurescontrasting

confidence: 79%

“…In a previous study conducted in China, the methylation status of 10 selected genes among them, ABCC6, BRCA1, CDH1, GDF15, HSPA2, RASSF1A, SALL3, THBS1, TMEFF2, and VIM was tested during the detection of BC and UTUC. Results suggested a sensitivity and speci city of 0.82 and 0.68 respectively among the UTUC cohort, which was insu cient for clinical application [18] .…”

Section: Introductionmentioning

confidence: 98%

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A Urine-Based Liquid Biopsy Method for Detection of Upper Tract Urinary Carcinoma

et al. 2020

Preprint

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Background: Conventional clinical detection methods such as CT, urine cytology, and ureteroscopy display low sensitivity and/or are invasive in the diagnosis of upper tract urinary carcinoma (UTUC), a factor precluding their use. Previous studies on urine biopsy have not shown satisfactory sensitivity and specificity in the application of both gene mutation or gene methylation panels. Therefore, these unfavorable factors call for an urgent need for a sensitive and non-invasive method for the diagnosis of UTUC.Methods: In this study, a total of 161 hematuria patients were enrolled with (n=69) or without (n=92) UTUC. High-throughput sequencing of 17 genes and methylation analysis for ONECUT2 CpG sites were combined as a liquid biopsy test panel. Further, a logistic regression prediction model that contained several significant features was used to evaluate the risk of UTUC in these patients.Results: In total, 86 UTUC- and 64 UTUC+ case samples were enrolled for the analysis. A logistic regression analysis of significant features including age, the mutation status of TERT promoter and ONECUT2 methylation level resulted inan optimal model with a sensitivity of 94.0%, a specificity of 93.1%, the positive predictive value of 92.2% and a negative predictive value of 94.7%. Notably, the area under the curve (AUC) was 0.957 in the training dataset while internal validation produced an AUC of 0.962. It is worth noting that during follow-up, a patient diagnosed with ureteral inflammation at the time of diagnosis exhibiting both positive mutation and methylation test results was diagnosed with ureteral carcinoma 17 months after his enrollment.Conclusion: This work utilized the epigenetic biomarker ONECUT2 for the first time in the detection of UTUC and discovered its superior performance. To improve its sensitivity, we combined the biomarker with a high-throughput sequencing of 17 genes test. It was found that the selected logistic regression model diagnosed with ureteral cancerThetcan evaluate upper tract urinary carcinoma risk of patients with hematuria and outperform other existing panels in providing clinical recommendations for the diagnosis of UTUC. Moreover, its high negative predictive value is conducive to rule to exclude patients without UTUC.

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Section: Univariate Logistic Regression Of Signi Cant Featurescontrasting

confidence: 79%

Section: Introductionmentioning

confidence: 98%

A Urine-Based Liquid Biopsy Method for Detection of Upper Tract Urinary Carcinoma

et al. 2020

Preprint

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“…Supplementary materials can be found at . References [63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98,99,100,101,102,103,104,105,106,107,108,109,110,111] are cited in the supplementary materials.…”

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confidence: 99%

DNA-Methylation-Based Detection of Urological Cancer in Urine: Overview of Biomarkers and Considerations on Biomarker Design, Source of DNA, and Detection Technologies

Larsen

Lind

Guldberg

et al. 2019

IJMS

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Changes in DNA methylation have been causally linked with cancer and provide promising biomarkers for detection in biological fluids such as blood, urine, and saliva. The field has been fueled by genome-wide characterization of DNA methylation across cancer types as well as new technologies for sensitive detection of aberrantly methylated DNA molecules. For urological cancers, urine is in many situations the preferred “liquid biopsy” source because it contains exfoliated tumor cells and cell-free tumor DNA and can be obtained easily, noninvasively, and repeatedly. Here, we review recent advances made in the development of DNA-methylation-based biomarkers for detection of bladder, prostate, renal, and upper urinary tract cancers, with an emphasis on the performance characteristics of biomarkers in urine. For most biomarkers evaluated in independent studies, there was great variability in sensitivity and specificity. We discuss issues that impact the outcome of DNA-methylation-based detection of urological cancer and account for the great variability in performance, including genomic location of biomarkers, source of DNA, and technical issues related to the detection of rare aberrantly methylated DNA molecules. Finally, we discuss issues that remain to be addressed to fully exploit the potential of DNA-methylation-based biomarkers in the clinic, including the need for prospective trials and careful selection of control groups.

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“…Also in urine sediments, methylation in p14ARF , p16INK4A , RASSF1A , DAPK , and APC showed a correlation with BC grade and stage (Pietrusiński et al, 2017). Guo et al used the methylation status for VIM , RASSF1A , GDF15 , and TMEFF2 to identify BC with 82% sensitivity and 53% specificity (Li et al, 2018b). RBBP8 has been identified as almost exclusively hypermethylated in BC (Mijnes et al, 2018), while Chen et al showed CDH13 methylation as a biomarker with prognostic value for BC screening in urine samples (Ren et al, 2016).…”

Section: Epigenetic Alterations As Biomarkers In Bc: the Potential Usmentioning

confidence: 99%

Epigenetics of Bladder Cancer: Where Biomarkers and Therapeutic Targets Meet

et al. 2019

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Bladder cancer (BC) is the most common neoplasia of the urothelial tract. Due to its high incidence, prevalence, recurrence and mortality, it remains an unsolved clinical and social problem. The treatment of BC is challenging and, although immunotherapies have revealed potential benefit in a percentage of patients, it remains mostly an incurable disease at its advanced state. Epigenetic alterations, including aberrant DNA methylation, altered chromatin remodeling and deregulated expression of non-coding RNAs are common events in BC and can be driver events in BC pathogenesis. Accordingly, these epigenetic alterations are now being used as potential biomarkers for these disorders and are being envisioned as potential therapeutic targets for the future management of BC. In this review, we summarize the recent findings in these emerging and exciting new aspects paving the way for future clinical treatment of this disease.

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Detection of urothelial carcinoma, upper tract urothelial carcinoma, bladder carcinoma, and urothelial carcinoma with gross hematuria using selected urine-DNA methylation biomarkers: A prospective, single-center study

Cited by 41 publications

References 27 publications

A Urine-Based Liquid Biopsy Method for Detection of Upper Tract Urinary Carcinoma

A Urine-Based Liquid Biopsy Method for Detection of Upper Tract Urinary Carcinoma

DNA-Methylation-Based Detection of Urological Cancer in Urine: Overview of Biomarkers and Considerations on Biomarker Design, Source of DNA, and Detection Technologies

Epigenetics of Bladder Cancer: Where Biomarkers and Therapeutic Targets Meet

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