scholarly journals Biomarkers in Bladder Cancer: Present Status and Perspectives

2007 ◽  
Vol 2 ◽  
pp. 117727190700200 ◽  
Author(s):  
Wun-Jae Kim ◽  
Soongang Park ◽  
Yong-June Kim
Keyword(s):  
Gene Expression ◽  
Cancer Research ◽  
Bladder Cancer ◽  
Cancer Progression ◽  
Transitional Cell ◽  
Cancer Recurrence ◽  
Global Gene Expression ◽  
Cancer Therapies ◽  
Predictive Capacity ◽  
Specificity And Sensitivity

Bladder cancers are a mixture of heterogeneous cell populations, and numerous factors are likely to be involved in dictating their recurrence, progression and the patient's survival. For any candidate prognostic marker to have considerable clinical relevance, it must add some predictive capacity beyond that offered by conventional clinical and pathologic parameters. Here, the current situation in bladder cancer research with respect to identification of suitable prognostic markers is reviewed. A number of individual molecular markers that might predict bladder cancer recurrence and progression have been identified but many are not sufficiently sensitive or specific for the whole spectrum of bladder cancer diseases seen in routine clinical practice. These limitations have led to interest in other molecular parameters that could enable more accurate prognosis for bladder cancer patients. Of particular interest is the epigenetic silencing of tumor suppressor genes. Since the methylation of these genes can correlate with a poor prognosis, the methylation profile may represent a new biomarker that indicates the risk of transitional cell carcinoma development. In addition, bladder cancer research is likely to be revolutionized by high-throughput molecular technologies, which allow rapid and global gene expression analysis of thousands of tumor samples. Initial studies employing these technologies have considerably expanded our ability to classify bladder cancers with respect to their survivability. Future microarray analyses are likely to reveal particular gene expression signatures that predict the likelihood of bladder cancer progression and recurrence, as well as patient's survival and responsiveness to different anti-cancer therapies, with great specificity and sensitivity.

scholarly journals MYC regulates ribosome biogenesis and mitochondrial gene expression programs through interaction with Host Cell Factor-1

2020 ◽  
Author(s):  
Tessa M. Popay ◽  
Jing Wang ◽  
Clare M. Adams ◽  
Simona G. Codreanu ◽  
Stacy Sherrod ◽  
...  
Keyword(s):  
Gene Expression ◽  
Host Cell ◽  
Ribosome Biogenesis ◽  
Focal Point ◽  
Mitochondrial Gene ◽  
Expression Patterns ◽  
Global Gene Expression ◽  
Cancer Therapies ◽  
Host Cell Factor

ABSTRACTThe oncoprotein transcription factor MYC is a major driver of malignancy and a highly-validated but challenging target for development of anti-cancer therapies. Novel strategies to inhibit MYC may come from understanding the co-factors it uses to drive pro-tumorigenic gene expression programs, providing their role in MYC activity is understood. Here, we interrogate how one MYC co-factor, Host Cell Factor (HCF)-1, contributes to MYC activity in a Burkitt lymphoma setting. We identify genes connected to mitochondrial function and ribosome biogenesis as direct MYC/HCF-1 targets, and demonstrate how modulation of the MYC–HCF-1 interaction influences cell growth, metabolite profiles, global gene expression patterns, and tumor growth in vivo. This work defines HCF-1 as a critical MYC co-factor, places the MYC–HCF-1 interaction in biological context, and highlights HCF-1 as a focal point for development of novel anti-MYC therapies.

Immunodetection of androgen and estrogen a,b receptors in human urinary bladder cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15616-15616
Author(s):  
A. Gómez Pinillos ◽  
G. Bueno Serrano ◽  
S. Sacristán López ◽  
R. García González ◽  
C. Varona Crespo ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Western Blotting ◽  
Cancer Progression ◽  
Transitional Cell ◽  
Urinary Bladder Cancer ◽  
Tumor Grade ◽  
Chi Square ◽  
Primary Tumors ◽  
Female Ratio ◽  
Covalent Modifications

15616 Background: Bladder cancer predominates in males. Loss of androgen receptor (AR) has been associated with invasive and undifferentiated tumors but little is known about the role of hormonal receptors in this type of cancer. Methods: We evaluated samples from 41 nonconsecutive patients treated for bladder transitional cell carcinoma between 2001–2003. Immunohistochemistry was performed using anti-AR and anti-ER a,b antibodies on paraffin-embedded tumors from transurethral resections, nuclear expression was assessed. Western blotting for AR and pAKT were performed in 22 transurethral resections from nonconsecutive bladder cancer patients treated between 2004–2006. Chi-square and U Mann-Witney tests were performed. Results: Immunohistochemistry study: the male/female ratio was 9/1; 61% were noninvasive tumors (pTa, is,1) and 32% were invasive (pT2,3); 22% were G1 and 75% were G2,3. 95% were AR(+), 40% ERa(+) and 94% ERb(+). Significant differences in AR expression were observed between G1 78% and G2,3 tumors 100%, with a high grade tumor prevalence in the AR(+) tumors 81.6% p=0.046. No differences between ERa,b and differentiation were found. G2,3 tumors were predominantly ERb(+). AR was found in 92% noninvasive and in 100% invasive tumors p=0.53. No significant differences were found between invasiveness and ERa,b. Noninvasive tumors showed higher ERa,b expresión (54%, 95% respectively) than invasive tumors (20%, 91% respectively). Western blotting group: 54.5% were primary tumors and 45.5% were recidives. The noninvasive/invasive rate was 59/32%, the G1/G2,3 rate was 4.5/95.5%. 112, 250 and 160 kDa bands were found. AR/pAKT rate was 86.4/100%. 100% of invasive tumors and 86% G2,3 tumors were AR(+). No differences between pAKT, invasiveness, differentiation or AR expression were observed but recidivated tumors had a slight higher median expression level. Conclusions: AR is positively related to tumor grade and might be involved in bladder cancer progression. The profile of AR bands suggest covalent modifications, due to ubiquitin-mediated degradation or to activation mechanisms mediated by SUMO. Nuclear AR and the absence of bands under 90kDa suggest that activated protein is present in bladder cancer. pAKT/AR inhibitors could play a role for bladder cancer therapy. No significant financial relationships to disclose.

scholarly journals Do Standardised Prognostic Algorithms Reflect Local Practice? Application of EORTC Risk Tables for Non-Muscle Invasive (pTa/pT1) Bladder Cancer Recurrence and Progression in a Local Cohort

2011 ◽  
Vol 11 ◽  
pp. 751-759 ◽  
Author(s):  
Rajiv Pillai ◽  
Duolao Wang ◽  
Erik K. Mayer ◽  
Paul Abel
Keyword(s):  
Bladder Cancer ◽  
Cell Cancer ◽  
Transitional Cell ◽  
Cancer Recurrence ◽  
Risk Groups ◽  
Original Algorithm ◽  
Transitional Cell Cancer ◽  
Study Population ◽  
Muscle Invasive ◽  
Prognostic Data

A risk calculator algorithm to allow prediction of probabilities of 1- and 5-year recurrence and progression rates in individuals with pTa/pT1 bladder cancer has been proposed by the European Organisation for Research and Treatment of Cancer (EORTC) and was incorporated into the European Association of Urology guidelines in 2006. We attempted to validate this algorithm in a cohort of patients with known outcome. Prognostic data were collected from a consecutively presenting cohort of 109 patients with non-muscle invasive (pTa/pT1) transitional cell cancer (TCC) at a single institution between 1983 and 1985. Using the same statistical models as in the EORTC original paper, predicted probabilities of 1- and 5-year recurrence and progression were calculated. Patients were divided into four risk groups for recurrence (Ir-IVr) and progression (Ip-IVp), respectively, using six prognostic criteria. These were then compared to the probabilities predicted in the EORTC algorithm. The predicted 1- and 5-year probabilities of recurrence were significantly higher in the study population as compared to the original EORTC algorithm for all four risk groups. The predicted 1-year probabilities for progression in groups Ip/IIIp and at 5-years for groups Ip/IIp were in accordance with the original algorithm, but were higher for the other progression groups. The concordance for the model of prediction using the study group for recurrence at 1 and 5 years was 62 and 63%, respectively, and for progression was 65 and 67, respectively. We were unable to validate the proposed algorithm in our group of patients. Although our study has limitations that prevent firm conclusions on the validity of the algorithm, it does expose some of the drawbacks of standardised nomograms when applied to local clinical practice.

Expression Signature of E2F1 and Its Associated Genes Predict Superficial to Invasive Progression of Bladder Tumors

2010 ◽  
Vol 28 (16) ◽  
pp. 2660-2667 ◽  
Author(s):  
Ju-Seog Lee ◽  
Sun-Hee Leem ◽  
Sang-Yeop Lee ◽  
Sang-Cheol Kim ◽  
Eun-Sung Park ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bladder Cancer ◽  
Cancer Progression ◽  
Gene Expression Data ◽  
Gene Expression Signature ◽  
Molecular Signature ◽  
Expression Data ◽  
Bladder Tumors ◽  
Expression Signature ◽  
Leave One Out

Purpose In approximately 20% of patients with superficial bladder tumors, the tumors progress to invasive tumors after treatment. Current methods of predicting the clinical behavior of these tumors prospectively are unreliable. We aim to identify a molecular signature that can reliably identify patients with high-risk superficial tumors that are likely to progress to invasive tumors. Patients and Methods Gene expression data were collected from tumor specimens from 165 patients with bladder cancer. Various statistical methods, including leave-one-out cross-validation methods, were applied to identify a gene expression signature that could predict the likelihood of progression to invasive tumors and to test the robustness of the expression signature in an independent cohort. The robustness of the gene expression signature was validated in an independent (n = 353) cohort. Results Supervised analysis of gene expression data revealed a gene expression signature that is strongly associated with invasive bladder tumors. A molecular classifier based on this gene expression signature correctly predicted the likelihood of progression of superficial tumor to invasive tumor. Conclusion We present a molecular signature that can predict, at diagnosis, the likelihood of bladder cancer progression and, possibly, lead to improvements in patient therapy.

scholarly journals Differential Gene Expression in Bladder Tumors from Workers Occupationally Exposed to Arylamines

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Ramya T. Kolli ◽  
Zongli Xu ◽  
Vijayalakshmi Panduri ◽  
Jack A. Taylor
Keyword(s):  
Gene Expression ◽  
Bladder Cancer ◽  
Occupational Exposure ◽  
Cancer Progression ◽  
Epithelial To Mesenchymal Transition ◽  
Occupational Exposures ◽  
Bladder Tumors ◽  
Mesenchymal Transition ◽  
Custom Panel

Occupational exposure to the arylamines benzidine and β-naphthylamine increase bladder cancer risk up to 100-fold, making them some of the most powerful human carcinogens. We hypothesize that tumors arising in people with occupational exposures have different patterns of gene expression than histologically similar tumors from people without such exposures. In a case-case study, we compare gene expression in 22 formalin-fixed paraffin-embedded (FFPE) bladder tumors from men with high-level occupational exposure to arylamines to that in 26 FFPE bladder tumors from men without such exposure. Gene expression analysis was performed on the NanoString nCounter system using a PanCancer Progression Panel comprised of 740 cancer progression-related genes and a custom panel of 69 arylamine- and bladder cancer-related genes which were chosen from in vitro studies. Although fold differences were small, there was evidence of differential expression by exposure status for 17 genes from the Progression Panel and 4 genes from the custom panel. In total, 10 genes showed dose-response association at a p < 0.01 , of which 4 genes (CD46, NR4A1, BAX, and YWHAZ) passed a false discovery rate (FDR) q value cutoff of 0.05 but were not significant after Bonferroni correction. Overall, we find limited evidence for differentially expressed genes in pathways related to DNA damage signaling and epithelial-to-mesenchymal transition (EMT).

scholarly journals Characterization of Uptake and Internalization of Exosomes by Bladder Cancer Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Carrie A. Franzen ◽  
Patricia E. Simms ◽  
Adam F. Van Huis ◽  
Kimberly E. Foreman ◽  
Paul C. Kuo ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Internal Standard ◽  
Cancer Recurrence ◽  
High Recurrence Rate ◽  
Bladder Cancer Cells ◽  
Cancer Cell Survival

Bladder tumors represent a special therapeutic challenge as they have a high recurrence rate requiring repeated interventions and may progress to invasive or metastatic disease. Exosomes carry proteins implicated in bladder cancer progression and have been implicated in bladder cancer cell survival. Here, we characterized exosome uptake and internalization by human bladder cancer cells using Amnis ImageStreamX, an image cytometer. Exosomes were isolated by ultracentrifugation from bladder cancer culture conditioned supernatant, labeled with PKH-26, and analyzed on the ImageStreamX with an internal standard added to determine concentration. Exosomes were cocultured with bladder cancer cells and analyzed for internalization. Using the IDEAS software, we determined exosome uptake based on the number of PKH-26+ spots and overall PKH-26 fluorescence intensity. Using unlabeled beads of a known concentration and size, we were able to determine concentrations of exosomes isolated from bladder cancer cells. We measured exosome uptake by recipient bladder cancer cells, and we demonstrated that uptake is dose and time dependent. Finally, we found that uptake is active and specific, which can be partially blocked by heparin treatment. The characterization of cellular uptake and internalization by bladder cancer cells may shed light on the role of exosomes on bladder cancer recurrence and progression.

scholarly journals Identification of GSN and LAMC2 as Key Prognostic Genes of Bladder Cancer by Integrated Bioinformatics Analysis

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1809
Author(s):  
Jia-Lian Yang ◽  
Charles C. N. Wang ◽  
Jia-Hua Cai ◽  
Che-Yi Chou ◽  
Yu-Chao Lin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bladder Cancer ◽  
Transitional Cell Carcinoma ◽  
Cell Carcinoma ◽  
Lymphatic Metastasis ◽  
Transitional Cell ◽  
The Cancer Genome Atlas ◽  
Cancer Disease ◽  
Hub Gene ◽  
Grade 3

Bladder cancer is a common malignancy with mechanisms of pathogenesis and progression. This study aimed to identify the prognostic hub genes, which are the central modulators to regulate the progression and proliferation in the specific subtype of bladder cancer. The identification of the candidate hub gene was performed by weighted gene co-expression network analysis to construct a free-scale gene co-expression network. The gene expression profile of GSE97768 from the Gene Expression Omnibus database was used. The association between prognosis and hub gene was evaluated by The Cancer Genome Atlas database. Four gene-expression modules were significantly related to bladder cancer disease: the red module (human adenocarcinoma lymph node metastasis), the darkturquioise module (grade 2 carcinoma), the lightgreen module (grade 3 carcinoma), and the royalblue module (transitional cell carcinoma lymphatic metastasis). Based on betweenness centrality and survival analysis, we identified laminin subunit gamma-2 (LAMC2) in the grade 2 carcinoma, gelsolin (GSN) in the grade 3 carcinoma, and homeodomain-interacting protein kinase 2 (HIPK2) in the transitional cell carcinoma lymphatic metastasis. Subsequently, the protein levels of LAMC2 and GSN were respectively down-regulated and up-regulated in tumor tissue with the Human Protein Atlas (HPA) database. Our results suggested that LAMC2 and GSN are the central modulators to transfer information in the specific subtype of the disease.

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