The Application of Artificial Intelligence to Microarray Data: Identification of a Novel Gene Signature to Identify Bladder Cancer Progression

Catto, James W.F.; Abbod, Maysam F.; Wild, Peter J.; Linkens, D.A.; Pilarsky, Christian; Rehman, Ishtiaq; Rosario, Derek J.; Denzinger, Stefan; Burger, Maximilian; Stoehr, Robert; Knuechel, Ruth; Hartmann, Arndt; Hamdy, Freddie C.

doi:10.1016/j.eururo.2009.10.029

Cited by 54 publications

(32 citation statements)

References 27 publications

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“…These subtypes show distinct clinical outcomes and differ with respect to the expression and mutation frequency of certain cancer-related genes, such as FGFR3 , PIK3CA , and TP53 . In general, prognostic signature genes are selected by optimizing supervised predictive models in a training dataset and then validating in test datasets (22). Because of “the curse of dimensionality” (i.e., the number of genes is much larger than the number of samples), most of the selected genes are “passengers” rather than “driving genes” that are functionally related to prognosis (23).…”

Section: Introductionmentioning

confidence: 99%

E2F4 Program Is Predictive of Progression and Intravesical Immunotherapy Efficacy in Bladder Cancer

Cheng

Varn

Marsit

2015

Molecular Cancer Research

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Bladder cancer is a common malignant disease, with non–muscle-invasive bladder cancer (NMIBC) representing the majority of tumors. This cancer subtype is typically treated by transurethral resection. In spite of treatment, up to 70% of patients show local recurrences. Intravesical BCG (Bacillus Calmette-Guerin) immunotherapy has been widely used to treat NMIBC, but it fails to suppress recurrence of bladder tumors in up to 40% of patients. Therefore, the development of prognostic markers is needed to predict the progression of bladder cancer and the efficacy of intravesical BCG treatment. This study demonstrates the effectiveness of an E2F4 signature for prognostic prediction of bladder cancer. E2F4 scores for each sample in a bladder cancer expression dataset were calculated by summarizing the relative expression levels of E2F4 target genes identified by ChIP-seq, and then the scores were used to stratify patients into good- and poor-outcome groups. The molecular signature was investigated in a single bladder cancer dataset and then its effectiveness was confirmed in two meta-bladder datasets consisting of specimens from multiple independent studies. These results were consistent in different datasets and demonstrate that the E2F4 score is predictive of clinical outcomes in bladder cancer, with patients whose tumors exhibit an E2F4 score >0 having significantly shorter survival times than those with an E2F4 score <0, in both non–muscle-invasive, and muscle-invasive bladder cancer. Furthermore, although intravesical BCG immunotherapy can significantly improve the clinical outcome of NMIBC patients with positive E2F4 scores (E2F4>0 group), it does not show significant treatment effect for those with negative scores (E2F4<0 group). Implications The E2F4 signature can be applied to predict the progression/recurrence and the responsiveness of patients to intravesical BCG immunotherapy in bladder cancer.

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Section: Introductionmentioning

confidence: 99%

E2F4 Program Is Predictive of Progression and Intravesical Immunotherapy Efficacy in Bladder Cancer

Cheng

Varn

Marsit

2015

Molecular Cancer Research

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“…Multiple molecular urinary biomarkers have been investigated to date, but none are sufficiently robust to enter clinical practice (Zwarthoff 2008). Many biomarkers fail as they are unable to detect both low and high-grade UCC, which are characterised by distinct molecular pathways and share few molecular alterations (Catto et al , 2005, 2009, 2010). Biomarker panels that assess molecular events characteristic of low- and high-grade UCC improve the accuracy of urinary tests, but are laborious (van Rhijn et al , 2003).…”

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An evaluation of urinary microRNA reveals a high sensitivity for bladder cancer

et al. 2012

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Background:Urinary biomarkers are needed to improve the care and reduce the cost of managing bladder cancer. Current biomarkers struggle to identify both high and low-grade cancers due to differing molecular pathways. Changes in microRNA (miR) expression are seen in urothelial carcinogenesis in a phenotype-specific manner. We hypothesised that urinary miRs reflecting low- and high-grade pathways could detect bladder cancers and overcome differences in genetic events seen within the disease.Methods:We investigated urinary samples (n=121) from patients with bladder cancer (n=68) and age-matched controls (n=53). Fifteen miRs were quantified using real-time PCR.Results:We found that miR is stable within urinary cells despite adverse handling and detected differential expression of 10 miRs from patients with cancer and controls (miRs−15a/15b/24-1/27b/100/135b/203/212/328/1224, ANOVA P<0.05). Individually, miR-1224-3p had the best individual performance with specificity, positive and negative predictive values and concordance of 83%, 83%, 75% and 77%, respectively. The combination of miRs-135b/15b/1224-3p detected bladder cancer with a high sensitivity (94.1%), sufficient specificity (51%) and was correct in 86% of patients (concordance).Conclusion:The use of this panel in patients with haematuria would have found 94% of urothelial cell carcinoma, while reducing cystoscopy rates by 26%. However, two invasive cancers (3%) would have been missed.

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“…Auch kombinierte Ansätze aus Genomics und Proteomics wurden beim Harnblasenkarzinom angewandt (eine Arbeit beschreibt eine dezidierte Signatur für prognostisch ungünstige Tumore [43]). Gemein ist diesen beiden hochinteressanten Ansätzen jedoch, dass die Reproduzierbarkeit und Stabilität der Resultate in Frage gestellt werden und scheinbar deutlich von der Heterogenität der Tumore beeinflusst werden [44], zudem bedarf die Interpretation teils aufwändiger Methoden [45]. …”

Section: Genom-und Proteomprofil: Das Große Ganzeunclassified

Nutzung von Markersystemen in der Behandlung des Harnblasenkarzinoms

Burger

Dorp

2011

Urologe

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Accepted prognostic factors for urothelial carcinomas of the bladder are tumor grade, T category, and in cases of muscle invasive carcinoma lymph node status. These morphological criteria correlate in general with the clinical course of patients suffering from bladder cancer. Beside histomorphological criteria the search for prognostic markers independent of histological evaluation seems to be important as the clinical course of bladder cancer patients can be very heterogeneous. For this purpose we reviewed the current literature and focussed on additional molecular markers with prognostic relevance.

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The Application of Artificial Intelligence to Microarray Data: Identification of a Novel Gene Signature to Identify Bladder Cancer Progression

Abstract: word count: 257 2 AbstractBackground: New methods to identify bladder cancer progression are required. Gene-

Cited by 54 publications

References 27 publications

E2F4 Program Is Predictive of Progression and Intravesical Immunotherapy Efficacy in Bladder Cancer

E2F4 Program Is Predictive of Progression and Intravesical Immunotherapy Efficacy in Bladder Cancer

An evaluation of urinary microRNA reveals a high sensitivity for bladder cancer

Nutzung von Markersystemen in der Behandlung des Harnblasenkarzinoms

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