Applications of array technology: identification of molecular targets in bladder cancer

Sänchez‐Carbayo, Marta; Cordon‐Cardo, Carlos

doi:10.1038/sj.bjc.6601406

Cited by 47 publications

(25 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although gene expression has been extensively profiled in bladder tumor tissue samples, little is known about its correlation with gene expression profiles of urine samples. To this end, using microarrays, we identified a high number of differentially expressed genes between UCC and control samples as well as between low-grade (LG) and high-grade (HG) bladder tumors, in accordance with many other studies (6,7,13,14). But more interestingly, we showed that these differentially expressed genes could also be identified in urine samples by real-time quantitative reversetranscription PCR (qRT-PCR; ref.…”

supporting

confidence: 56%

Gene Expression Signature in Urine for Diagnosing and Assessing Aggressiveness of Bladder Urothelial Carcinoma

Mengual

Burset

Ribal

et al. 2010

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: To develop an accurate and noninvasive method for bladder cancer diagnosis and prediction of disease aggressiveness based on the gene expression patterns of urine samples.Experimental Design: Gene expression patterns of 341 urine samples from bladder urothelial cell carcinoma (UCC) patients and 235 controls were analyzed via TaqMan Arrays. In a first phase of the study, three consecutive gene selection steps were done to identify a gene set expression signature to detect and stratify UCC in urine. Subsequently, those genes more informative for UCC diagnosis and prediction of tumor aggressiveness were combined to obtain a classification system of bladder cancer samples. In a second phase, the obtained gene set signature was evaluated in a routine clinical scenario analyzing only voided urine samples.Results: We have identified a 12+2 gene expression signature for UCC diagnosis and prediction of tumor aggressiveness on urine samples. Overall, this gene set panel had 98% sensitivity (SN) and 99% specificity (SP) in discriminating between UCC and control samples and 79% SN and 92% SP in predicting tumor aggressiveness. The translation of the model to the clinically applicable format corroborates that the 12+2 gene set panel described maintains a high accuracy for UCC diagnosis (SN = 89% and SP = 95%) and tumor aggressiveness prediction (SN = 79% and SP = 91%) in voided urine samples.Conclusions: The 12+2 gene expression signature described in urine is able to identify patients suffering from UCC and predict tumor aggressiveness. We show that a panel of molecular markers may improve the schedule for diagnosis and follow-up in UCC patients. Clin Cancer Res; 16(9); 2624-33.

show abstract

supporting

confidence: 56%

Gene Expression Signature in Urine for Diagnosing and Assessing Aggressiveness of Bladder Urothelial Carcinoma

Mengual

Burset

Ribal

et al. 2010

Clinical Cancer Research

View full text Add to dashboard Cite

show abstract

“…At the present time, there is no single molecular marker that provides 100% accuracy in predicting tumor behavior (43,45,49), and as a result molecular prognostication is moving toward a multiplex-marker setting. This is particularly true for microarray-based approaches that use multi-gene molecular classifiers (50,51). Several studies have applied genomic microarray technology to gain insight into the changes in expression profiles that occur during different stages of bladder cancer progression, generating disease classifiers and outcome predictors by using several key genes to built a multi-marker molecular signature that is significantly associated with pathological stage, tumor grade, and overall survival (52)(53)(54).…”

Section: The Transcriptional Regulator Ppar␥ Is Not Responsible For Lmentioning

confidence: 99%

Loss of Expression of the Adipocyte-type Fatty Acid-binding Protein (A-FABP) Is Associated with Progression of Human Urothelial Carcinomas

Ohlsson

Moreira

Gromov

et al. 2005

Molecular & Cellular Proteomics

View full text Add to dashboard Cite

Bladder cancer is the second most common genitourinary tumor and the fourth most common solid malignancy in Denmark, with an incidence of 1,200 -1,300 patients per year and a mortality rate of ϳ300. It encompasses a large variety of histological heterogeneous tumor types arising predominantly in the epithelium (urothelium) lining of the urinary bladder and the ureters. Tumor types of the urothelium include urothelial carcinomas (UCs), 1 squamous cell carcinomas, adenocarcinomas, as well as other less frequent lesions (1). UCs account for more than 90% of the bladder carcinomas and comprise a wide spectrum of lesions with distinct biological and functional characteristics. Up to 80% of patients with superficial bladder cancer lesions will recur, and of these ϳ25% will progress to invasive disease (2). A major challenge today is to identify the subset of low-grade lesions that may recur and evolve into muscle invasive and subsequently to metastatic disease.Presently, the most reliable prognostic factors for recurrence and progression are grading and staging. These parameters, however, cannot predict with certainty the long-term outcome of the disease, and as a result it is important to devise strategies to identify biomarkers that may predict tumor behavior and clinical outcome. Several prognostic markers have been identified, some of which, like p53 and pRB, have a long-standing association with bladder cancer (3, 4). The product of the retinoblastoma gene (pRB) is a main regulator of cell-cycle progression, while p53 exerts its function as a key DNA checkpoint molecule, triggering growth arrest or apoptotic processes in response to DNA aberrations and cellular stress. pRB and p53 are frequently altered in bladder From the ‡Department

show abstract

“…In particular, the cancer epigenome alterations better characterized in bladder cancer include global changes in DNA methylation, altered histone modification, and miRNAs patterns [7,[31][32][33][34][35][36][37][38][39][40]. Because epigenetic features such as global DNA hypomethylation and promoter-specific hypermethylation can be commonly observed in benign neoplasias and early-stage tumors, it is becoming apparent that epigenetic deregulation may precede preliminary transforming events such as mutations in tumor suppressors, protooncogenes, or both, and genomic instability [6].…”

Section: Epigenetic Factors Contribute To Bladder Cancer Tumorigenesimentioning

confidence: 98%

“…In fact, these "epimutations" sometimes provide the second hit for cancer initiation postulated by the two-hit model, as they can silence the remaining active allele of previously mutated tumor suppressors [1]. A few studies have explored the link between the methylation patterns observed in bladder cancer with the expression of these proteins [28,29], as compared to studies assessing candidate-driven hypermethylation [30][31][32][33][34][35][36][37][38][39][40]. The disturbance of the DNA methylation landscape in transformed cells has been recently supported by the finding of somatic mutations in DNMT3A in acute myeloid leukemia [41].…”

Section: Hypermethylation: a Relevant Epigenetic Modifications In Cancermentioning

confidence: 98%

“…It is an environmental disease driven by the multistep accumulation of molecular alterations at the DNA, RNA, and protein levels, among others. These molecular alterations result in uncontrolled cellular proliferation, cell cycle deregulation, decrease in cell death or apoptosis, blockage of differentiation, and invasion potentially leading to metastatic spread [31][32][33][34]. It is becoming evident that the epigenomic component plays an important role in the regulation of the expression of many critical genes participating in these pathways.…”

Section: Epigenetic Factors Contribute To Bladder Cancer Tumorigenesimentioning

confidence: 99%

See 1 more Smart Citation

Hypermethylation in bladder cancer: biological pathways and translational applications

Sänchez‐Carbayo

2012

Tumor Biol.

View full text Add to dashboard Cite

A compelling body of evidences sustains the importance of epigenetic mechanisms in the development and progression of cancer. Assessing the epigenetic component of bladder tumors is strongly improving our understanding of their biology and clinical behavior. In terms of DNA methylation, cancer cells show genome-wide hypomethylation and site-specific CpG island promoter hypermethylation. In the context of other epigenetic alterations, this review will focus on the hypermethylation of CpG islands in promoter regions, as the most widely described epigenetic modification in bladder cancer. CpG islands hypermethylation is believed to be critical in the transcriptional silencing and regulation of tumor suppressor and crucial cancer genes involved in the major molecular pathways controlling bladder cancer development and progression. In particular, several biological pathways of frequently methylated genes include cell cycle, DNA repair, apoptosis, and invasion, among others. Furthermore, translational aspects of bladder cancer methylomes described to date will be discussed towards their potential application as bladder cancer biomarkers. Several tissue methylation signatures and individual candidates have been evidenced, that could potentially stratify tumors histopathologically, and discriminate patients in terms of their clinical outcome. Tumor methylation profiles could also be detected in urinary specimens showing a promising role as non-invasive markers for cancer diagnosis towards an early detection and potentially for the surveillance of bladder cancer patients in a near future. However, the epigenomic exploration of bladder cancer has only just begun. Genome-scale DNA methylation profiling studies will further highlight the relevance of the epigenetic component to gain knowledge of bladder cancer biology and identify those profiles and candidates better correlating with clinical behavior.

show abstract

Applications of array technology: identification of molecular targets in bladder cancer

Cited by 47 publications

References 26 publications

Gene Expression Signature in Urine for Diagnosing and Assessing Aggressiveness of Bladder Urothelial Carcinoma

Gene Expression Signature in Urine for Diagnosing and Assessing Aggressiveness of Bladder Urothelial Carcinoma

Loss of Expression of the Adipocyte-type Fatty Acid-binding Protein (A-FABP) Is Associated with Progression of Human Urothelial Carcinomas

Hypermethylation in bladder cancer: biological pathways and translational applications

Contact Info

Product

Resources

About