Urinary Cell-Free DNA IQGAP3/BMP4 Ratio as a Prognostic Marker for Non–Muscle-Invasive Bladder Cancer

2019 ◽  
Vol 17 (3) ◽  
pp. e704-e711
Author(s):  
Yanjie Xu ◽  
Ye-Hwan Kim ◽  
Pildu Jeong ◽  
Xuan-Mei Piao ◽  
Young Joon Byun ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Prognostic Marker ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Cell Free Dna ◽  
Free Dna ◽  
Muscle Invasive

Superior molecular pathology of urothelial bladder cancer using urinary cell-free DNA.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 491-491
Author(s):  
Ruiyun Zhang ◽  
Feng Xie ◽  
Yue Zhang ◽  
Yiqiu Wang ◽  
Zhixin Zhao ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Molecular Pathology ◽  
Predictive Value ◽  
Invasive Bladder Cancer ◽  
Urothelial Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Cell Free Dna ◽  
Free Dna ◽  
Urothelial Bladder ◽  
Muscle Invasive

491 Background: Both urinary and blood cell-free DNA (cfDNA) have been implicated in noninvasive detection and surveillance of urothelial bladder cancer (UBC). However, a direct comparison of their diagnostic performance in the real-world setting is lacking. Methods: 59 eligible cases with pathologically confirmed disease and accompanying tissue/urine pairs were prospectively enrolled and consented to Institutional Review Board-approved protocols. Baseline peripheral blood mononuclear cell (PBMC) and plasma specimens were collected during clinic visit. The 180-gene Predicine liquid biopsy assay was applied for ultra-deep targeted sequencing and somatic alteration identification in tumor tissue-based DNA (tDNA), urinary cfDNA (ucfDNA) and blood cfDNA (bcfDNA). Results: The 59 studied subjects constituted a natural UBC cohort of non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC), including 48 (81.4%) NMIBC and 42 (71.2%) male patients. Diverse quantitative metrics such as VAF (variant allele frequency) and TMB (tumor mutational burden) were invariably concordant between tDNA and ucfDNA, but not bcfDNA. The mutational landscape captured by tDNA or ucfDNA highly resembled each other and mirrored previously described genomic panorama of UBC, whereas a significant proportion of bcfDNA aberrations stemmed from clonal hematopoiesis. Using tDNA-informed variants as the ground truth, ucfDNA assays achieved a specificity of 99.3%, a sensitivity of 86.7%, a positive predictive value (PPV) of 67.2%, a negative predictive value (NPV) of 99.8%, and a diagnostic accuracy of 99.1%, which were generally lower in the case of bcfDNA analysis. Conclusions: Urine-based molecular pathology provides valid and complete genetic information about neoplastic lesions, and represents a faithful surrogate for genotyping and monitoring UBC.

scholarly journals FAM70Bas a Novel Prognostic Marker for Cancer Progression and Cancer-Specific Death in Muscle-Invasive Bladder Cancer

2012 ◽  
Vol 53 (9) ◽  
pp. 598 ◽  
Author(s):  
Ho-Won Kang ◽  
Hyung-Yoon Yoon ◽  
Yun-Sok Ha ◽  
Won Tae Kim ◽  
Yong-June Kim ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Prognostic Marker ◽  
Cancer Progression ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive

scholarly journals Integrative Transcriptome Profiling Reveals SKA3 as a Novel Prognostic Marker in Non-Muscle Invasive Bladder Cancer

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4673
Author(s):  
Chaelin You ◽  
Xuan-Mei Piao ◽  
Keunsoo Kang ◽  
Yong-June Kim ◽  
Kyuho Kang
Keyword(s):  
Bladder Cancer ◽  
Cancer Patients ◽  
Rna Sequencing ◽  
Clinical Outcomes ◽  
Prognostic Marker ◽  
Transcriptome Profiling ◽  
Invasive Bladder Cancer ◽  
Cell Subpopulation ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive

Approximately 80% of all new bladder cancer patients are diagnosed with non-muscle invasive bladder cancer (NMIBC). However, approximately 15% of them progress to muscle-invasive bladder cancer (MIBC), for which prognosis is poor. The current study aimed to improve diagnostic accuracy associated with clinical outcomes in NMIBC patients. Nevertheless, it has been challenging to identify molecular biomarkers that accurately predict MIBC progression because this disease is complex and heterogeneous. Through integrative transcriptome profiling, we showed that high SKA3 expression is associated with poor clinical outcomes and MIBC progression. We performed RNA sequencing on human tumor tissues to identify candidate biomarkers in NMIBC. We then selected genes with prognostic significance by analyzing public datasets from multiple cohorts of bladder cancer patients. We found that SKA3 was associated with NMIBC pathophysiology and poor survival. We analyzed public single-cell RNA-sequencing (scRNA-seq) data for bladder cancer to dissect transcriptional tumor heterogeneity. SKA3 was expressed in an epithelial cell subpopulation expressing genes regulating the cell cycle. Knockdown experiments confirmed that SKA3 promotes bladder cancer cell proliferation by accelerating G2/M transition. Hence, SKA3 is a new prognostic marker for predicting NMIBC progression. Its inhibition could form part of a novel treatment lowering the probability of bladder cancer progression.

Evaluating cell cycle progression score as a prognostic marker for non-muscle invasive bladder cancer (NMIBC).

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 476-476
Author(s):  
Christopher J. Weight ◽  
Paari J Murugan ◽  
David Chesla ◽  
Resha Tejpaul ◽  
Ayman Soubra ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Bladder Cancer ◽  
Prognostic Marker ◽  
Cell Cycle Progression ◽  
Multivariable Analysis ◽  
Invasive Bladder Cancer ◽  
Prognostic Information ◽  
Muscle Invasive Bladder Cancer ◽  
Cycle Progression ◽  
Muscle Invasive

476 Background: Accurate grading and staging from transurethral resection of bladder tumors (TURBT) is vital for appropriate clinical management. Non-muscle-invasive bladder cancer (NMIBC) can recur progress with higher grade and or stage progression to MIBC, requiring radical intervention with poorer prognosis. Further, grade and stage may change in 20-50% of TURBTs following re-review by expert GU pathologists Objective measures of stage and grade might offer additional and/or improved risk stratification; therefore we evaluated a molecular RNA signature as a prognostic marker for NMIBC. Methods: Patients were diagnosed with NMIBC at the University of Minnesota (UM)or Spectrum Health System(SHS) from 2005-2012. A Cell Cycle Progression (CCP) score was determined from the average expression of 36 CCP genes for patients with available FFPE diagnostic TURBT. The combined cohort consisted of 293 patients (UM n = 152, SHS n = 141). Study outcome was time from NMIBC diagnosis to progression to MIBC. Median follow-up for patients who did not experience an event was 4.4 years for UM and 6.9 for SHS. Association with outcomes was evaluated by Cox proportional hazards survival analysis and likelihood ratio tests. All analyses were stratified by cohort. Results: CCP score was associated with progression to MIBC in univariable analysis [hazard ratio 1.42 (95% CI 1.19, 1.68), p = 4.3x10-5]. Tumor grade and stage were also highly prognostic. CCP score was strongly associated with stage (T1 vs Ta, p < 10-6) and grade (high vs low, p < 10-14) in both cohorts. As a result, CCP score did not provide independent prognostic information in multivariable analysis after adjusting for stage and grade (p = 0.32). There was a significant interaction between stage and CCP score (p = 0.0017), justifying an exploratory analysis of CCP score in Ta disease. In this subset, CCP score trended toward (p = 0.056) after adjusting for grade. Conclusions: In NMIBC, CCP score was highly correlated with tumor stage and grade and could serve as a quantitative measure of clinical parameters. The score may also provide prognostic information regarding risk of progression to MIBC, particularly in patients with Ta disease, but requires additional validation.

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