scholarly journals Urinary Cell-Free DNA in Bladder Cancer Detection

Diagnostics ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 306
Author(s):  
Ryan Tsz-Hei Tse ◽  
Hongda Zhao ◽  
Christine Yim-Ping Wong ◽  
Carol Ka-Lo Cheng ◽  
Angel Wing-Yan Kong ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Detection ◽  
Urinary Bladder Cancer ◽  
Molecular Classification ◽  
Cell Free Dna ◽  
Molecular Features ◽  
Promising Tool ◽  
Free Dna ◽  
Genetic Features ◽  
Muscle Invasive

Urinary bladder cancer is a common urological cancer. Although flexible cystoscopy is widely employed in bladder cancer detection, it is expensive, invasive, and uncomfortable to the patients. Recently, urinary cell-free DNA (ucfDNA) isolated from urine supernatant has been shown to have great potential in bladder cancer detection and surveillance. Molecular features, such as integrity and concentration of ucfDNA, have been shown to be useful for differentiating bladder cancer patients from healthy controls. Besides, bladder cancer also exhibits unique genetic features that can be identified from sequencing and expression of ucfDNA. Apart from bladder cancer detection, ucfDNA is also useful for molecular classification. For example, ucfDNA exhibits significant differences, both molecularly and genetically, in non-muscle-invasive and muscle-invasive bladder cancers. There is no doubt that ucfDNA is a very promising tool for future applications in the field of bladder cancer.

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

scholarly journals Squamous Cell Carcinoma of the Urinary Bladder: Clinicopathological and Molecular Update

2021 ◽  
Author(s):  
Sunil Vitthalrao Jagtap ◽  
Swati S Jagtap ◽  
Parneet Kaur ◽  
Snigdha Vartak
Keyword(s):  
Squamous Cell Carcinoma ◽  
Bladder Cancer ◽  
Urinary Bladder ◽  
Urothelial Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Urinary Bladder Cancer ◽  
Cell Phenotype ◽  
Molecular Features ◽  
Muscle Invasive

Urinary bladder cancer is one of the most prevalent cancers worldwide.Squamous Cell Carcinoma (SCC) is an uncommon subtype of urinary bladder carcinoma.It is a malignant epithelial neoplasm arising in the urinary bladder demonstrating a pure squamous cell phenotype. On histopathology it is considered when tumor is showing pure squamous morphology without any component of conventional urothelial carcinoma. The SCC is a histologically distinct form of cancer. It arises from the uncontrolled multiplication of cells showing particular cytological or tissue architectural characteristics of squamous cell differentiation, such as the presence of keratin, tonofilament bundles or desmosomes. Majority of bladder SCC are high grade, high stage tumors with most cancers having muscle invasion at the time of diagnosis while overall about 80% of bladder cancers are non-muscle invasive bladder cancer at diagnosis.COX-2 is markedly expressed in all SCCs. An increased COX-2 level induces the development of SCC of the bladder affecting many biological features of this tissue including apoptosis, cell adhesion, angiogenesis and invasiveness.TERT promoter mutations, commonly found in conventional urothelial carcinoma, are also highly prevalent in urinary bladder squamous cell carcinoma suggesting a common tumorgenesis and potential utility as a molecular urine-based-screening assay.This review summarizes the current features related to clinical , pathological, and molecular features of SCC of urinary bladder.

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 Deoxyribonucleic Acid 5-Hydroxymethylation in Cell-Free Deoxyribonucleic Acid, a Novel Cancer Biomarker in the Era of Precision Medicine

2021 ◽  
Vol 9 ◽  
Author(s):  
Ling Xu ◽  
Yixin Zhou ◽  
Lijie Chen ◽  
Abdul Saad Bissessur ◽  
Jida Chen ◽  
...  
Keyword(s):  
Cancer Detection ◽  
Deoxyribonucleic Acid ◽  
Basic Research ◽  
Active Role ◽  
Dna Demethylation ◽  
Precision Oncology ◽  
Aberrant Methylation ◽  
Cell Free Dna ◽  
Promising Tool ◽  
Free Dna

Aberrant methylation has been regarded as a hallmark of cancer. 5-hydroxymethylcytosine (5hmC) is recently identified as the ten-eleven translocase (ten-eleven translocase)-mediated oxidized form of 5-methylcytosine, which plays a substantial role in DNA demethylation. Cell-free DNA has been introduced as a promising tool in the liquid biopsy of cancer. There are increasing evidence indicating that 5hmC in cell-free DNA play an active role during carcinogenesis. However, it remains unclear whether 5hmC could surpass classical markers in cancer detection, treatment, and prognosis. Here, we systematically reviewed the recent advances in the clinic and basic research of DNA 5-hydroxymethylation in cancer, especially in cell-free DNA. We further discuss the mechanisms underlying aberrant 5hmC patterns and carcinogenesis. Synergistically, 5-hydroxymethylation may act as a promising biomarker, unleashing great potential in early cancer detection, prognosis, and therapeutic strategies in precision oncology.

scholarly journals Liquid Biopsy Analysis of FGFR3, TERT Promoter and STAG2 Hotspot Mutations for Disease Surveillance in Bladder Cancer

2020 ◽  
pp. 1-7
Author(s):  
Victor Romanov ◽  
Dimitri Gnatenko ◽  
Edward Forsyth ◽  
Liang Xiaohui ◽  
Olga Povcher ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Sensitivity And Specificity ◽  
Liquid Biopsy ◽  
Disease Surveillance ◽  
Digital Pcr ◽  
Cell Free Dna ◽  
Free Dna ◽  
Tert Promoter ◽  
Mutational Status ◽  
Muscle Invasive

Patients with non-muscle invasive bladder cancer (NMIBC) are followed by frequent cystoscopies. Innovative approaches partly replacing cystoscopy (uncomfortable, expensive, low sensitive procedure) are demanded. The current study aims to establish a fast, reliable, non-invasive, and inexpensive procedure for NMIBC patient surveillance. Liquid biopsy is a reliable source of biomarkers for cancer patient monitoring. Urine is the most suitable biological liquid to search for bladder cancer biomarkers. Cell-free DNA in urine represents tumor-related mutations for several cancers, including the bladder. We investigated mutations in FGFR3, TERT promoter, and STAG2 as markers for diagnostics and follow-up in NMIBC. Digital PCR was used to detect mutations in urine-derived cell-free DNA. The sensitivity and specificity of the markers in relation to clinical outcomes served as criteria of the assay efficiency. The sensitivity with a single marker (TERT) reached 87%, with a specificity of 77%. Combining two biomarkers (TERT+FGFR3) increased the specificity of the assay to 100% with a sensitivity of 72%. Different mutational status of STAG2 can indicate NMIBC presence or recurrence. Therefore, applying the suggested combination of biomarkers with simple detection procedures to larger patient cohorts will allow developing procedures for BC detection and surveillance with optimal sensitivity and specificity. Based on the results of this proof-in-concept study, we conclude that this simple, fast and inexpensive assay can add diagnostic and prognostic value to cystoscopy/cytology analysis of NMIBC patients.

scholarly journals Long non-coding RNAs to predict postoperative recurrence in muscle-invasive bladder cancer and to develop a new molecular classification system

2021 ◽  
Author(s):  
Zhiyong Li ◽  
LIJUAN JIANG ◽  
ZHILING ZHANG ◽  
MINHUA DENG ◽  
WENSU WEI ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Classification System ◽  
Growth Factor Receptor ◽  
Molecular Classification ◽  
Postoperative Recurrence ◽  
Invasive Bladder Cancer ◽  
Chemotherapy Response ◽  
Muscle Invasive Bladder Cancer ◽  
Molecular Features ◽  
Muscle Invasive

Abstract Background: Reliable molecular markers are much needed for early prediction of recurrence in muscle-invasive bladder cancer (MIBC) patients. We aimed to build an lncRNA signature to improve recurrence prediction and lncRNA-based molecular classification of MIBC. Methods: LncRNAs of 320 MIBC patients from TCGA database were analyzed, and a nomogram was established. A molecular classification system was created, and immunotherapy, chemotherapy response prediction, immune score analysis, immunoinfiltration analysis, and mutational data analysis were conducted. Results: An eight-lncRNA signature could classify the patients into high- and low-risk subgroups having significantly different DFS. Our samples validated that the 8 lncRNAs were related with DFS. The nomogram achieved a C-index of 0.719 (95% CI, 0.674–0.764). Time-dependent ROC analyses indicated the superior prognostic accuracy of nomograms for DFS prediction (0.76, 95% CI, 0.697–0.807). Further, four clusters with different DFS and molecular features were identified. The four clusters (median DFS = 11.8, 15.3, 17.9, and 18.9 months, respectively) showed a high frequency of TTN, fibroblast growth factor receptor-3, TP53, and TP53 mutations, respectively. They were enriched with macrophages M2, T cells CD8, macrophages M0, and macrophages M0, respectively. Clusters 2 and 3 demonstrated potential sensitivity to immunotherapy and insensitivity to chemotherapy, whereas cluster 4 showed potential insensitivity to immunotherapy and sensitivity to chemotherapy. Conclusion: Our lncRNA-based signature proved to be a reliable prognostic tool to determine postoperative recurrence in MIBC patients. We believe that the four molecular subtypes possess the potential to guide treatment.

scholarly journals Circulating Cell-Free DNA in Liquid Biopsies as Potential Biomarker for Bladder Cancer: A Review

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1448
Author(s):  
Raquel Herranz ◽  
Julia Oto ◽  
Emma Plana ◽  
Álvaro Fernández-Pardo ◽  
Fernando Cana ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Progression ◽  
Specific Treatment ◽  
Predictive Biomarkers ◽  
Liquid Biopsies ◽  
Cell Free Dna ◽  
Specific Patient ◽  
Free Dna ◽  
Potential Biomarker ◽  
Cancer Types

Bladder cancer (BC) is among the most frequent cancer types in the world and is the most lethal urological malignancy. Presently, diagnostic and follow-up methods for BC are expensive and invasive. Thus, the identification of novel predictive biomarkers for diagnosis, progression, and prognosis of BC is of paramount importance. To date, several studies have evidenced that cell-free DNA (cfDNA) found in liquid biopsies such as blood and urine may play a role in the particular scenario of urologic tumors, and its analysis may improve BC diagnosis report about cancer progression or even evaluate the effectiveness of a specific treatment or anticipate whether a treatment would be useful for a specific patient depending on the tumor characteristics. In the present review, we have summarized the up-to-date studies evaluating the value of cfDNA as potential diagnostic, prognostic, or monitoring biomarker for BC in several biofluids.

CancerEMC: frontline non-invasive cancer screening from circulating protein biomarkers and mutations in cell-free DNA

2021 ◽  
Author(s):  
Saifur Rahaman ◽  
Xiangtao Li ◽  
Jun Yu ◽  
Ka-Chun Wong
Keyword(s):  
Test Data ◽  
Cancer Detection ◽  
Blood Test ◽  
Class Imbalance ◽  
Cancer Type ◽  
Protein Biomarkers ◽  
Class Imbalance Problem ◽  
Multiple Cancer ◽  
Cell Free Dna ◽  
Free Dna

Abstract Motivation The early detection of cancer through accessible blood tests can foster early patient interventions. Although there are developments in cancer detection from cell-free DNA (cfDNA), its accuracy remains speculative. Given its central importance with broad impacts, we aspire to address the challenge. Methods A bagging Ensemble Meta Classifier (CancerEMC) is proposed for early cancer detection based on circulating protein biomarkers and mutations in cfDNA from the blood. CancerEMC is generally designed for both binary cancer detection and multi-class cancer type localization. It can address the class imbalance problem in multi-analyte blood test data based on robust oversampling and adaptive synthesis techniques. Results Based on the clinical blood test data, we observe that the proposed CancerEMC has outperformed other algorithms and state-of-the-arts studies (including CancerSEEK published in Science, 2018) for cancer detection. The results reveal that our proposed method (i.e., CancerEMC) can achieve the best performance result for both binary cancer classification with 99.1748% accuracy (AUC = 0.999) and localized multiple cancer detection with 74.1214% accuracy (AUC = 0.938). For addressing the data imbalance issue with oversampling techniques, the accuracy can be increased to 91.4966% (AUC = 0.992), where the state-of-the-art method can only be estimated at 69.64% (AUC = 0.921). Similar results can also be observed on independent and isolated testing data. Availability https://github.com/saifurcubd/Cancer-Detection

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