scholarly journals Molecular Pathways in Low and High-grade Non-muscle Invasive Bladder Cancer as Revealed by Several OMICs Data Analyses

2021 ◽  
Vol 1 (1) ◽  
Author(s):  
Somaye Zareian ◽  
Saghar Pahlavanneshan
Keyword(s):  
Bladder Cancer ◽  
Data Analysis ◽  
Microarray Data ◽  
Microarray Data Analysis ◽  
Low Grade ◽  
Molecular Pathways ◽  
High Grade ◽  
Hub Genes ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive

Background: Bladder cancer is one of the most prevalent cancers, accounting for 2.1% of cancer mortalities worldwide. Bladder cancer is categorized into non-muscle invasive and muscle-invasive bladder cancers. Non-muscle invasive bladder cancer (NMIBC) is the most common and widely heterogeneous type with different outcomes. Objectives: This study was designed to categorize NMIBC tumor grade based on microarray data analysis. Methods: We performed microarray data analysis using GSE7476, GSE13507, and GSE37815 in patients diagnosed with NMIBC. Differentially expressed genes (DEGs) were identified based on low-grade and high-grade NMIBC. Protein-protein interaction (PPI) network analysis was carried out, and hub genes and underlying molecular pathways were identified. Results: We observed low-grade Hub genes, including GAS6, TGFB3, TPM1, COL5A1, COL1A2, SERPING1, ACTA2, TPM2, SDC1, and A2M involved in a variety of gene ontology (GO) biological processes, while high-grade genes were involved in cell cycle and cell division. The most relevant pathways suggested for low-grade NMIBC were extracellular matrix organization, platelet degranulation, and muscle contraction. Conclusions: The identification of gene hubs and underlying pathways in several low and high-grade NMIBC samples may offer better treatment management and prognostication based on molecular profiling.

scholarly journals A Single-Institutional Study of Human Immunodeficiency Virus-Related Bladder Cancer

2021 ◽  
Author(s):  
Mengmeng Zhang ◽  
Yanyan Zhang ◽  
Zhiqiang Zhu ◽  
Yu Zhang
Keyword(s):  
Bladder Cancer ◽  
Cancer Patients ◽  
Clinical Characteristics ◽  
Transitional Cell ◽  
Invasive Bladder Cancer ◽  
Low Grade ◽  
High Grade ◽  
Muscle Invasive Bladder Cancer ◽  
Tumor Pathology ◽  
Muscle Invasive

Abstract Purpose: We wished to investigate the clinical characteristics, treatments for tumor, pathology and outcomes of bladder cancer patients with HIV-infected.Patients and methods: We identified 10 cases of bladder cancer with HIV-infected from 2015 to 2020.We retrospectively investigated the clinical characteristics of the cases including demographic information, clinical presentation, TNM stage and so on. We investigated treatments for tumor, pathology, outcomes and HIV-relevant parameters during patients’ hospitalization course as well. Results: In our study, it was astonished to find that bladder cancer patients with HIV-infected were males at the median age of 51 years old, and no females were diagnosed on the contrary. Nine (90%)patients presented with painless gross hematuria, while one patient with incidental findings on ultrasonic examination. Six(60%) patients co-infected with another kind of infectious disease, four with syphilis, and two with HBV respectively. The median CD4+ T-lymphocyte cell count was 493/ul withthin 2 weeks prior to the diagnosis bladder cancer. Cystoscope examination manifested that the lesions were located in the trigonum of the bladder in four(40%)patients. All patients underwent surgeries successfully, six underwent transurethral resection of bladder tumor(TURBT),two of whom relapsed once, and one underwent TURBT twice due to recurrence and then RC and urethrectomy because of urethral invasion. All non muscle-invasive bladder cancer(NMIBC)patients received intravesical chemotherapy with pirarubicin 30mg for at least half year conventionally, and only one patient occurred mild adverse reaction of irritative symptoms of bladder. Pathologic analysis documented that all patients(100%) had transitional cell carcinoma(TCC). Tumor grade classification showed that three cases were identified with low grade TCC, and six cases with high grade or invasive TCC, two of whom occurred recurrence for once or twice respectively. One patient was identified with low grade TCC of primary tumor and high grade TCC of recurrent focal(Figure 2).Five cases(50%) were ascertained as (NMIBC) with pT1N0M0, while the rest five patients(50%) were muscle-invasive bladder cancer(MIBC) with at least pT2N0M0. During the median follow-up of 56 months (range from 5 months to 68 months) six cases(five were MIBC patients )died due to distant metastases. No patients acceptted adjuvent immunotherapy mainly due to the role of PD-1+ T cells in HIV transcription in treated aviremic individuals, concerns of unknown adverse effects and economic factors.Conclusions: It seemed like that bladder caner patients had higher tumor stage and more aggressive pathology. we did not find any evidence on the relationship between immunodeficiency and cancer progression because of relatively stable HIV status of this crew in our study. MIBC patients with HIV-infected really have worse outcomes, and more attention is warranted to pay to this special population in this situation when they present with hematuria extraordinarily.

Comprehensive targeted gene profiling to determine the genomic signature likely to drive progression of high-grade nonmuscle invasive bladder cancer to muscle invasive bladder cancer.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 568-568
Author(s):  
Abedalrhman Alkhateeb ◽  
Govindaraja Atikukke ◽  
Lisa Porter ◽  
Bre-Anne Fifield ◽  
Dora Cavallo-Medved ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Gene Profiling ◽  
Invasive Bladder Cancer ◽  
Low Grade ◽  
Genomic Profiling ◽  
High Grade ◽  
Single Nucleotide Variants ◽  
Muscle Invasive Bladder Cancer ◽  
Non Invasive ◽  
Muscle Invasive

568 Background: Bladder cancer is the fifth most common cancer and eighth leading cause of cancer related-death in North America. It can present as non-muscle invasive bladder cancer (NMIBC) and/or muscle invasive bladder (MIBC). Although genomic profiling studies have established that low-grade NMIBC and MIBC are genetically distinct, high-grade NMIBC can recur and progress to MIBC [ Knowles, M.A. and C.D. Hurst, 2015]. Low grade, non-invasive bladder cancers are characterized by activating mutations in fibroblast growth factor receptor 3 (FGFR3), HRAS or other pathways of receptor kinase activation. High-grade disease, which is often becomes invasive, is characterized by inactivation of TP53 and Rb pathways [Kim, J., et al.]. Finding a subtype of invasive carcinoma with FGFR3 mutation may suggest an alternate pathway by which low grade, non-invasive pathology could transform into invasive disease [Knowles, M.A. and C.D. Hurst, 2015]. Methods: In this study, using a total of 30 bladder cancer (NMIBC and MIBC) patient samples from Windsor Regional Hospital Cancer Program, we performed comprehensive targeted gene sequencing to identify single nucleotide variants, small insertions / deletions, copy number variants and splice variants in over 500 common tumor genes panel. Results: Preliminary data from our study correlates with previously published mutation landscape for NMIBC and MIBC, and includes mutations in EGFR, FGFR3, FGFR4, PIK3CA, CDK6, ALK, JAK, as well as RET. While mutations in AKT1, BRCA1, CCND1, ERBB2, FGFR1, FGFR2, HRAS, and MET appear to be prevalent in NMIBC, mutations in IDH1 and MAP2K2 appear to be more common in MIBC. Three of the samples used in the study are from patients who progressed from high-grade NMIBC to MIBC. Conclusions: Therefore, have the genomic profiling performed at these two stages, which provides a unique ability to identify the potential “genomic triggers” for the transition.

scholarly journals Stem-Like Signature Predicting Disease Progression in Early Stage Bladder Cancer. The Role of E2F3 and SOX4

Biomedicines ◽  
2018 ◽  
Vol 6 (3) ◽  
pp. 85 ◽  
Author(s):  
Joaquim Bellmunt
Keyword(s):  
Stem Cells ◽  
Bladder Cancer ◽  
Cancer Stem Cells ◽  
Tumor Progression ◽  
Cell Types ◽  
Invasive Bladder Cancer ◽  
Low Grade ◽  
High Grade ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive

The rapid development of the cancer stem cells (CSC) field, together with powerful genome-wide screening techniques, have provided the basis for the development of future alternative and reliable therapies aimed at targeting tumor-initiating cell populations. Urothelial bladder cancer stem cells (BCSCs) that were identified for the first time in 2009 are heterogenous and originate from multiple cell types; including urothelial stem cells and differentiated cell types—basal, intermediate stratum and umbrella cells Some studies hypothesize that BCSCs do not necessarily arise from normal stem cells but might derive from differentiated progenies following mutational insults and acquisition of tumorigenic properties. Conversely, there is data that normal bladder tissues can generate CSCs through mutations. Prognostic risk stratification by identification of predictive markers is of major importance in the management of urothelial cell carcinoma (UCC) patients. Several stem cell markers have been linked to recurrence or progression. The CD44v8-10 to standard CD44-ratio (total ratio of all CD44 alternative splicing isoforms) in urothelial cancer has been shown to be closely associated with tumor progression and aggressiveness. ALDH1, has also been reported to be associated with BCSCs and a worse prognosis in a large number of studies. UCC include low-grade and high-grade non-muscle invasive bladder cancer (NMIBC) and high-grade muscle invasive bladder cancer (MIBC). Important genetic defects characterize the distinct pathways in each one of the stages and probably grades. As an example, amplification of chromosome 6p22 is one of the most frequent changes seen in MIBC and might act as an early event in tumor progression. Interestingly, among NMIBC there is a much higher rate of amplification in high-grade NMIBC compared to low grade NMIBC. CDKAL1, E2F3 and SOX4 are highly expressed in patients with the chromosomal 6p22 amplification aside from other six well known genes (ID4, MBOAT1, LINC00340, PRL, and HDGFL1). Based on that, SOX4, E2F3 or 6q22.3 amplifications might represent potential targets in this tumor type. Focusing more in SOX4, it seems to exert its critical regulatory functions upstream of the Snail, Zeb, and Twist family of transcriptional inducers of EMT (epithelial–mesenchymal transition), but without directly affecting their expression as seen in several cell lines of the Cancer Cell Line Encyclopedia (CCLE) project. SOX4 gene expression correlates with advanced cancer stages and poor survival rate in bladder cancer, supporting a potential role as a regulator of the bladder CSC properties. SOX4 might serve as a biomarker of the aggressive phenotype, also underlying progression from NMIBC to MIBC. The amplicon in chromosome 6 contains SOX4 and E2F3 and is frequently found amplified in bladder cancer. These genes/amplicons might be a potential target for therapy. As an existing hypothesis is that chromatin deregulation through enhancers or super-enhancers might be the underlying mechanism responsible of this deregulation, a potential way to target these transcription factors could be through epigenetic modifiers.

scholarly journals Diagnostic value comparison of CellDetect, fluorescent in situ hybridization (FISH), and cytology in urothelial carcinoma

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Donghao Shang ◽  
Yuting Liu ◽  
Xiuhong Xu ◽  
Zhenghao Chen ◽  
Daye Wang
Keyword(s):  
Bladder Cancer ◽  
In Situ Hybridization ◽  
Fluorescent In Situ Hybridization ◽  
Urine Cytology ◽  
Low Grade ◽  
High Grade ◽  
Muscle Invasive Bladder Cancer ◽  
Significant Difference ◽  
Muscle Invasive

Abstract Background To evaluate the clinical effectiveness of a novel CellDetect staining technique, compared with fluorescent in situ hybridization (FISH), and urine cytology, in the diagnosis of urothelial carcinoma (UC). Methods A total of 264 patients with suspicious UC were enrolled in this study. All tissue specimens were collected by biopsy or surgery. Urine specimen was obtained for examinations prior to the surgical procedure. CellDetect staining was carried out with CellDetect kit, and FISH was performed with UroVysion detection kit, according to the manufacturer’s instructions. For urine cytology, all specimens were centrifuged using the cytospin method, and the slides were stained by standard Papanicolaou stain. Results In this study, there were 128 cases of UC and 136 cases of non-UC, with no significant difference in gender and age between the two groups. Results for sensitivity of CellDetect, FISH, and urine cytology were 82.8%, 83.6%, and 39.8%, respectively. The specificity of the three techniques were 88.2%, 90.4%, and 86.0%, respectively. The sensitivity of CellDetect and FISH are significantly superior compared to the conventional urine cytology; however, there was no significant difference in specificity among three staining techniques. In addition, the sensitivity of CellDetect in lower urinary tract UC, upper urinary tract UC, non-muscle-invasive bladder cancer (NMIBC), and muscle-invasive bladder cancer (MIBC) were 83.3%, 81.8%, 83.5%, and 72.0%, respectively. The screening ability of CellDetect has no correlation with tumor location and the tumor stage. The sensitivity of CellDetect in low-grade UC and high-grade UC were 51.6 and 92.8%. Thus, screening ability of CellDetect in high-grade UC is significantly superior compared to that in low-grade UC. Conclusions CellDetect and FISH show equal value in diagnosing UC, both are superior to conventional urine cytology. Compared to FISH, CellDetect is cost effective, easy to operate, with extensive clinical application value to monitor recurrence of UC, and to screen indetectable UC.

Risk-specific intensity of surveillance practices in non-muscle-invasive bladder cancer: Results from the BCAN/SUO/AUA/LUGPA electronic survey.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 251-251
Author(s):  
A. Smith ◽  
M. E. Nielsen ◽  
J. Ferguson ◽  
A. Manvar ◽  
R. Pruthi ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Lower Risk ◽  
Invasive Bladder Cancer ◽  
Low Grade ◽  
High Grade ◽  
Muscle Invasive Bladder Cancer ◽  
Electronic Survey ◽  
Muscle Invasive ◽  
Intensive Surveillance ◽  
The Ideal

251 Background: The ideal surveillance regimen for patients with non-muscle-invasive bladder cancer (NMIBC) is uncertain. Given different grade- and stage-specific risks of recurrence and progression, there is some question whether it might be acceptable to pursue less intensive surveillance practices for patients with lower risk disease, and there is a paucity of data on current patterns of care in this area of practice. Methods: An electronic survey was developed by the Bladder Cancer Advocacy Network (BCAN) to elicit self-reported practices of cystoscopy, cytology, and radiographic testing in the setting of surveillance for patients with a history of NMIBC. The survey was circulated to urologists via the AUA, SUO and LUGPA distribution lists. 512 respondents completed the survey. Results: Among respondents, 66% report performing cystoscopy every 3 months on all patients for at least the first two years following diagnosis of NMIBC. The remaining 33% report performing surveillance cystoscopy less frequently, 95% of whom report doing so in the setting of low grade pathology. Similarly, 51% report using cytology with every cystoscopy, 23% do so for all high grade cases, and 30% report not using cytology with every cystoscopy. In the absence of recurrence for patients with an initial high grade diagnosis, upper tract reimaging is performed annually in 48%, biannually in 37% and never in 3%. The corresponding figures for patients with an index diagnosis of low grade disease are 14%, 37% and 28%, respectively. In the event of a recurrence in the bladder, 80% of respondents report reimaging the upper tracts for patients with high grade disease, versus 45% in the event of a low grade recurrence. Conclusions: A substantial number of urologists responding to a survey report using relatively less intensive surveillance practices in patients with lower risk NMIBC. These results suggest a lack of consensus on the ideal intensity of evaluation in this setting, and provide a basis for prospective studies to validate the safest and most cost-effective strategies for surveillance. No significant financial relationships to disclose.

Quality of transurethral resection in patients with bladder cancer: A process-outcomes link.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 292-292
Author(s):  
Eric Christian Ballon-Landa ◽  
Karim Chamie ◽  
Jeffrey C. Bassett ◽  
Timothy J. Daskivich ◽  
Meryl Leventhal ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Transurethral Resection ◽  
Invasive Bladder Cancer ◽  
Low Grade ◽  
Detrusor Muscle ◽  
High Grade ◽  
Muscle Invasive Bladder Cancer ◽  
Cancer Specific Survival ◽  
Muscle Invasive ◽  
Pathology Reports

292 Background: Detrusor muscle at diagnostic transurethral resection of a bladder tumor (TURBT) is often used as a surrogate of resection quality. We examined whether surgical and pathologic quality at the time of initial resection was associated with improved cancer-specific survival among subjects diagnosed with non-muscle-invasive bladder cancer. Methods: We retrospectively reviewed the operative and pathology reports of all individuals ≥18 years of age within the Los Angeles SEER registry, with an incident diagnosis of urothelial non-muscle-invasive bladder cancer between 2004-2005. We recorded patient age, gender, race, marital status, socioeconomic status, insurance type, institution type, surgeon and pathologist volume, tumor stage and grade, detrusor muscle presence/mention, and vital status. After adjusting for confounding using competing-risks regression analysis, we determined whether surgical and pathologic quality was associated with cancer-specific survival. Results: We identified 1,865 patients, 335 urologists, and 278 pathologists. Muscle was reported as present in 972 (52.1%), reported as absent in 564 (30.2%), and was not mentioned in 329 (17.7%) of the initial pathology reports. The incidence of detrusor muscle sampling did not differ according to grade or stage. However, bladder cancer death was more likely with higher stage disease (Tis: HR=5.00, 95% CI 2.38-10.50; T1: HR=5.44, 95% CI 3.00-9.88) and lower quality staging (muscle absent: HR=1.50, CI 1.00-2.27; muscle not mentioned: HR=2.01, CI 1.14-3.56). This pattern was enhanced among those with high-grade disease. For this group, the 5-year cancer-specific mortality was 8.0%, 13.0%, and 21.5% when muscle was present, absent, or not mentioned, respectively. Conclusions: Nearly half of all diagnostic TURBTs do not include muscle. This omission is associated with increased mortality, particularly in high-grade disease—yet few of these patients undergo treatment to correct this error. Because urologists cannot discern between high- or low-grade disease, we contend that all patients with bladder cancer should undergo endoscopic resection with detrusor muscle sampling (and appropriate pathology reporting) at diagnosis.

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