MP68-04 A FIVE—GENE DNA—METHYLATION BIOMARKER PANEL SENSITIVELY DETECTS BLADDER CANCER AND DISCRIMINATES BETWEEN HIGH—GRADE AND LOW—GRADE DISEASE IN VOIDED URINE

2015 ◽  
Vol 193 (4S) ◽  
Author(s):  
Thomas Hermanns ◽  
Ekaterina Olkhov-Mitsel ◽  
Andrea Savio ◽  
Bethany Gill ◽  
Jenna Sykes ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Bladder Cancer ◽  
Low Grade ◽  
High Grade ◽  
Biomarker Panel

scholarly journals A urine-based DNA methylation assay to facilitate early detection and risk stratification of bladder cancer

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Weimei Ruan ◽  
Xu Chen ◽  
Ming Huang ◽  
Hong Wang ◽  
Jiaxin Chen ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Bladder Cancer ◽  
Risk Stratification ◽  
Early Stage ◽  
Operative Risk ◽  
Low Grade ◽  
Single Center ◽  
Detection Model ◽  
Methylation Assay ◽  
Muscle Invasive

Abstract Background Current non-invasive tests have limited sensitivities and lack capabilities of pre-operative risk stratification for bladder cancer (BC) diagnosis. We aimed to develop and validate a urine-based DNA methylation assay as a clinically feasible test for improving BC detection and enabling pre-operative risk stratifications. Methods A urine-based DNA methylation assay was developed and validated by retrospective single-center studies in patients of suspected BC in Cohort 1 (n = 192) and Cohort 2 (n = 98), respectively. In addition, a prospective single-center study in hematuria patient group (Cohort 3, n = 174) was used as a second validation of the model. Results The assay with a dual-marker detection model showed 88.1% and 91.2% sensitivities, 89.7% and 85.7% specificities in validation Cohort 2 (patients of suspected BC) and Cohort 3 (patients of hematuria), respectively. Furthermore, this assay showed improved sensitivities over cytology and FISH on detecting low-grade tumor (66.7–77.8% vs. 0.0–22.2%, 0.0–22.2%), Ta tumor (83.3% vs. 22.2–41.2%, 44.4–52.9%) and non-muscle invasive BC (NMIBC) (80.0–89.7% vs. 51.5–52.0%, 59.4–72.0%) in both cohorts. The assay also had higher accuracies (88.9–95.8%) in diagnosing cases with concurrent genitourinary disorders as compared to cytology (55.6–70.8%) and FISH (72.2–77.8%). Meanwhile, the assay with a five-marker stratification model identified high-risk NMIBC and muscle invasive BC with 90.5% sensitivity and 86.8% specificity in Cohort 2. Conclusions The urine-based DNA methylation assay represents a highly sensitive and specific approach for BC early-stage detection and risk stratification. It has a potential to be used as a routine test to improve diagnosis and prognosis of BC in clinic.

EPCO-17. METHYLATION ANALYSIS OF MATCHED PRIMARY AND RECURRENT IDHmt ASTROCYTOMA; AN UPDATE FROM THE GLIOMA LONGITUDINAL ANALYSIS NL (GLASS-NL) CONSORTIUM

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi5-vi5
Author(s):  
Wies Vallentgoed ◽  
Anneke Niers ◽  
Karin van Garderen ◽  
Martin van den Bent ◽  
Kaspar Draaisma ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Surgical Resection ◽  
Molecular Mechanisms ◽  
Relative Proportion ◽  
Low Grade ◽  
High Grade ◽  
Primary Tumors ◽  
Genome Wide ◽  
Dna Methylation Profiling ◽  
Methylation Profiling

Abstract The GLASS-NL consortium, was initiated to gain insight into the molecular mechanisms underlying glioma evolution and to identify markers of progression in IDH-mutant astrocytomas. Here, we present the first results of genome-wide DNA-methylation profiling of GLASS-NL samples. 110 adult patients were identified with an IDH-mutant astrocytoma at first diagnosis. All patients underwent a surgical resection of the tumor at least twice, separated by at least 6 months (median 40.9 months (IQR: 24.0, 64.7). In 37% and 18% of the cases, patients were treated with radiotherapy or chemotherapy respectively, before surgical resection of the recurrent tumor. DNA-methylation profiling was done on 235 samples from 103 patients (102 1st, 101 2nd, 29 3rd, and 3 4th resection). Copy number variations were also extracted from these data. Methylation classes were determined according to Capper et al. Overall survival (OS) was measured from date of first surgery. Of all primary tumors, the methylation-classifier assigned 85 (87%) to the low grade subclass and 10 (10%) to the high grade subclass. The relative proportion of high grade tumors increased ~three-fold at tumor recurrence (32/101, 32%) and even further in the second recurrence (15/29, 52%). Methylation classes were prognostic, both in primary and recurrent tumors. The overall DNA-methylation levels of recurrent samples was lower than that of primary samples. This difference is explained by the increased number of high grade samples at recurrence, since near identical DNA-methylation levels were observed in samples that remained low grade. In an unsupervised analysis, DNA-methylation data derived from primary and first recurrence samples of individual patients mostly (79%) cluster together. Recurrent samples that do not cluster with their primary tumor, form a separate group with relatively low genome-wide DNA-methylation. Our data demonstrate that methylation profiling identifies a shift towards a higher grade at tumor progression coinciding with reduced genome-wide DNA-methylation levels.

scholarly journals PD-1 and PD-L1 are more highly expressed in high-grade bladder cancer than in low-grade cases: PD-L1 might function as a mediator of stage progression in bladder cancer

BMC Urology ◽  
2018 ◽  
Vol 18 (1) ◽  
Author(s):  
Takashi Kawahara ◽  
Yukari Ishiguro ◽  
Shinji Ohtake ◽  
Ikuma Kato ◽  
Yusuke Ito ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Low Grade ◽  
High Grade ◽  
Stage Progression

scholarly journals Effectiveness of contrast-enhanced ultrasound for detecting the staging and grading of bladder cancer: a systematic review and meta-analysis

2020 ◽  
Author(s):  
Xinyue Ge ◽  
Zhong-Kai Lan ◽  
Jing Chen ◽  
Shang-Yong Zhu
Keyword(s):  
Bladder Cancer ◽  
Diagnostic Accuracy ◽  
Likelihood Ratio ◽  
Positive Likelihood Ratio ◽  
Cochrane Library ◽  
Forest Plot ◽  
Low Grade ◽  
High Grade ◽  
Contrast Enhanced Ultrasound ◽  
Contrast Enhanced

Aim: The study retrospectively analysed the accuracy of preoperative contrast-enhanced ultrasound (CEUS) in differenti-ating stage Ta-T1 or low-grade bladder cancer (BC) from stage T2 or high-grade bladder cancer. Material and methods: We systematically searched the literature indexed in PubMed, Embase, and the Cochrane Library for original diagnostic articles of bladder cancer. The diagnostic accuracy of CEUS was compared with cystoscopy and/or transurethral resection of bladder tumors (TURBT). The bivariate logistic regression model was used for data pooling, couple forest plot, diagnostic odds ratio (DOR) and summary receiver operating characteristic (SROC). Results: Five studies met the selection criteria; the overall number of reported bladder cancers patients were 436. The pooled-sensitivity (P-SEN), pooled-specificity (P-SPE), pooled-positive likelihood ratio (PLR+), pooled-negative likelihood ratio (PLR−), DOR, and area under the SROC curve were 94.0% (95%CI: 85%–98%), 90% (95%CI: 83%–95%), 9.5 (95%CI: 5.1–17.6), 0.06 (95%CI: 0.02–0.17), 147 (95%CI: 35–612) and 97% (95% CI: 95%–98%) respectively. Conclusion: CEUS reaches a high efficiency in discriminating Ta-T1 or low-grade bladder cancer from stage T2 or high-grade bladder cancer. It can be a promising method in patients to distinguish T staging and grading of bladder cancer because of its high sensitivity, specificity and diagnostic accuracy.

scholarly journals Three serum metabolite signatures for diagnosing low-grade and high-grade bladder cancer

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Guangguo Tan ◽  
Haibo Wang ◽  
Jianlin Yuan ◽  
Weijun Qin ◽  
Xin Dong ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Low Grade ◽  
High Grade

Risk factors for bladder cancer recurrence survival in patients with upper-tract urothelial carcinoma

2018 ◽  
Vol 104 (6) ◽  
pp. 451-458 ◽  
Author(s):  
Yu-Peng Wu ◽  
Yun-Zhi Lin ◽  
Min-Yi Lin ◽  
Ting-Ting Lin ◽  
Shao-Hao Chen ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Urothelial Carcinoma ◽  
Cancer Recurrence ◽  
Cox Proportional Hazards Model ◽  
Upper Tract Urothelial Carcinoma ◽  
Intravesical Therapy ◽  
Low Grade ◽  
High Grade ◽  
Upper Tract ◽  
Bladder Cancer Recurrence

Purpose: The aim of this work was to investigate the predictive factors for bladder cancer recurrence survival (BCRS) in patients with upper-tract urothelial carcinoma (UTUC). Methods: We selected patients with UTUC who underwent segmental ureterectomy (Su) or nephroureterectomy (Nu) from 2004 to 2013 from the Surveillance, Epidemiology, and End Results (SEER) database. Patients with a history of intravesical therapy for bladder cancer and bladder cancer prior to the diagnosis of UTUC were excluded. We used Kaplan-Meier analysis, log-rank tests, and Cox proportional hazards model to compare overall survival, cancer-specific survival, and BCRS. Results: In a cohort of 1,454 patients, 169 (11.6%) had low-grade tumors and 1,285 (88.4%) had high-grade tumors; 239 (16.4%) underwent Su and 1,215 (83.6%) underwent Nu. We found that T4 grade (hazard ratio [HR] = 6.216; 95% confidence interval [CI], 3.197-12.087) and ureteral tumors (HR = 1.764; 95% CI, 1.173-2.652) were predictors of shorter BCRS, whereas Nu (HR = 0.608; 95% CI, 0.388-0.953) predicted longer BCRS. Five-year BCRS rates were low-grade tumors: 94.1%, high-grade tumors: 85.4% (p = 0.038); plus Su: 82.9%, and Nu: 87.6% (p = 0.016). Conclusions: Use of Su should be more selective for high-grade tumors, as it correlates with shorter BCRS. Tumors located in the ureter are associated with shorter BCRS than those located in the renal pelvis.

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