Package 'curatedBladderData'

Title: Bladder Cancer Gene Expression Analysis
Description: The curatedBladderData package provides relevant functions and data for gene expression analysis in patients with bladder cancer.
Authors: Markus Riester
Maintainer: Markus Riester <[email protected]>
License: Artistic-2.0
Version: 1.48.0
Built: 2026-10-10 11:07:01 UTC
Source: https://github.com/bioc/curatedBladderData

Help Index


Predictive value of progression-related gene classifier in primary non-muscle invasive bladder cancer.

Description

While several molecular markers of bladder cancer prognosis have been identified, the limited value of current prognostic markers has created the need for new molecular indicators of bladder cancer outcomes. The aim of this study was to identify genetic signatures associated with disease prognosis in bladder cancer.We used 272 primary bladder cancer specimens for microarray analysis and real-time reverse transcriptase polymerase chain reaction (RT-PCR) analysis. Microarray gene expression analysis of randomly selected 165 primary bladder cancer specimens as an original cohort was carried out. Risk scores were applied to stratify prognosis-related gene classifiers. Prognosis-related gene classifiers were individually analyzed with tumor invasiveness (non-muscle invasive bladder cancer [NMIBC] and muscle invasive bladder cancer [MIBC]) and prognosis. We validated selected gene classifiers using RT-PCR in the original (165) and independent (107) cohorts. Ninety-seven genes related to disease progression among NMIBC patients were identified by microarray data analysis. Eight genes, a progression-related gene classifier in NMIBC, were selected for RT-PCR. The progression-related gene classifier in patients with NMIBC was closely correlated with progression in both original and independent cohorts. Furthermore, no patient with NMIBC in the good-prognosis signature group experienced cancer progression.We identified progression-related gene classifier that has strong predictive value for determining disease outcome in NMIBC. This gene classifier could assist in selecting NMIBC patients who might benefit from more aggressive therapeutic intervention or surveillance.

Usage

data( GSE13507_eset )

Format

experimentData(eset):
Experiment data
  Experimenter name: Kim WJ, Kim EJ, Kim SK, Kim YJ et al. Predictive value of progression-related gene classifier in primary non-muscle invasive bladder cancer. Mol Cancer 2010 Jan 8;9:3. 
  Laboratory: Kim, Bae 2010 
  Contact information:  
  Title: Predictive value of progression-related gene classifier in primary non-muscle invasive bladder cancer. 
  URL:  
  PMIDs: 20059769 

  Abstract: A 223 word abstract is available. Use 'abstract' method.
  Information is available on: preprocessing 
  notes:
   platform_title:     
      Illumina human-6 v2.0 expression beadchip
   platform_shorttitle:     
      Illumina human-6 v2.0
   platform_summary:     
      illuminaHumanv2
   platform_manufacturer:     
      Illumina
   platform_distribution:     
      commercial
   platform_accession:     
      GPL6102
   platform_technology:     
      oligonucleotide beads

Preprocessing: default
featureData(eset):
An object of class 'AnnotatedDataFrame'
  featureNames: A1BG A1CF ... ZZZ3 (19329 total)
  varLabels: probeset gene
  varMetadata: labelDescription

Details

assayData: 19329 features, 255 samples
Platform type: illuminaHumanv2
Overall survival time-to-event summary (in years):
Call: survfit(formula = Surv(time, cens) ~ -1)

   90 observations deleted due to missingness 
records   n.max n.start  events  median 0.95LCL 0.95UCL 
 165.00  165.00  165.00   69.00    7.26    5.53      NA 

--------------------------- 
Available sample meta-data: 
--------------------------- 

alt_sample_name: 
   Length     Class      Mode 
      255 character character 

sample_type: 
adjacentnormal        healthy     metastatic          tumor 
            58             10             22            165 

summarystage: 
   invasive superficial        NA's 
         62         103          90 

T: 
   Min. 1st Qu.  Median    Mean 3rd Qu.    Max.    NA's 
  0.000   1.000   1.000   1.473   2.000   4.000      90 

N: 
   0    1    2    3 NA's 
 133    8    4    1  109 

M: 
   0    1 NA's 
 157    8   90 

age: 
   Min. 1st Qu.  Median    Mean 3rd Qu.    Max.    NA's 
  24.00   59.00   66.00   65.18   73.00   88.00      90 

gender: 
   f    m NA's 
  30  135   90 

adjuvant_chemo: 
   n    y NA's 
 138   27   90 

days_to_death: 
   Min. 1st Qu.  Median    Mean 3rd Qu.    Max.    NA's 
     31     521    1113    1473    2258    4169      90 

vital_status: 
deceased   living     NA's 
      69       96       90 

dfs_event: 
 doc  dod  ned NA's 
  37   32   96   90 

uncurated_author_metadata: 
   Length     Class      Mode 
      255 character character 


Bladder cancer outcome and subtype classification by gene expression.

Description

Models of bladder tumor progression have suggested that genetic alterations may determine both phenotype and clinical course. We have applied expression microarray analysis to a divergent set of bladder tumors to further elucidate the course of disease progression and to classify tumors into more homogeneous and clinically relevant subgroups. cDNA microarrays containing 10,368 human gene elements were used to characterize the global gene expression patterns in 80 bladder tumors, 9 bladder cancer cell lines, and 3 normal bladder samples. Robust statistical approaches accounting for the multiple testing problem were used to identify differentially expressed genes. Unsupervised hierarchical clustering successfully separated the samples into two subgroups containing superficial (pT(a) and pT(1)) versus muscle-invasive (pT(2)-pT(4)) tumors. Supervised classification had a 90.5% success rate separating superficial from muscle-invasive tumors based on a limited subset of genes. Tumors could also be classified into transitional versus squamous subtypes (89% success rate) and good versus bad prognosis (78% success rate). The performance of our stage classifiers was confirmed in silico using data from an independent tumor set. Validation of differential expression was done using immunohistochemistry on tissue microarrays for cathepsin E, cyclin A2, and parathyroid hormone-related protein. Genes driving the separation between tumor subsets may prove to be important biomarkers for bladder cancer development and progression and eventually candidates for therapeutic targeting.

Usage

data( GSE1827_eset )

Format

experimentData(eset):
Experiment data
  Experimenter name: Blaveri E, Simko JP, Korkola JE, Brewer JL, Baehner F, Mehta K, Devries S, Koppie T, Pejavar S, Carroll P, Waldman FM. Bladder cancer outcome and subtype classification by gene expression.Clin Cancer Res. 2005 Jun 1;11(11):4044-55. 
  Laboratory: Blaveri, Waldman 2005 
  Contact information:  
  Title: Bladder cancer outcome and subtype classification by gene expression. 
  URL:  
  PMIDs: 15930339 

  Abstract: A 216 word abstract is available. Use 'abstract' method.
  Information is available on: preprocessing 
  notes:
   platform_title:     
      JAKE
   platform_shorttitle:     
      JAKE
   platform_summary:     
      JAKE
   platform_manufacturer:     
      other
   platform_distribution:     
      non-commercial
   platform_accession:     
      GPL1479
   platform_technology:     
      spotted DNA/cDNA

Preprocessing: default
featureData(eset):
An object of class 'AnnotatedDataFrame'
  featureNames: A2M AADAC ... ZZEF1 (6225 total)
  varLabels: probeset gene
  varMetadata: labelDescription

Details

assayData: 6225 features, 80 samples
Platform type: JAKE
Overall survival time-to-event summary (in years):
Call: survfit(formula = Surv(time, cens) ~ -1)

records   n.max n.start  events  median 0.95LCL 0.95UCL 
 80.000  80.000  80.000  44.000   2.301   0.978      NA 

--------------------------- 
Available sample meta-data: 
--------------------------- 

alt_sample_name: 
   Min. 1st Qu.  Median    Mean 3rd Qu.    Max. 
   44.0   360.0   452.5   425.1   513.2   591.0 

sample_type: 
tumor 
   80 

surgery_type: 
   rc turbt 
   50    30 

histological_type: 
squamous      tcc 
       6       74 

summarygrade: 
high  low 
  67   13 

summarystage: 
   invasive superficial 
         53          27 

T: 
 0  1  2  3  4 
17 10 14 26 13 

N: 
   0    1    2 NA's 
  29    6   11   34 

M: 
   0    1 NA's 
   3    2   75 

age: 
   Min. 1st Qu.  Median    Mean 3rd Qu.    Max.    NA's 
  28.00   57.25   66.00   65.56   73.00  113.00       2 

gender: 
 f  m 
24 56 

recurrence_status: 
norecurrence   recurrence         NA's 
          49           24            7 

days_to_death: 
   Min. 1st Qu.  Median    Mean 3rd Qu.    Max. 
    4.0   217.5   386.0   842.2  1280.0  4348.0 

vital_status: 
deceased   living 
      44       36 

uncurated_author_metadata: 
   Length     Class      Mode 
       80 character character 


Combined gene expression and genomic profiling define two intrinsic molecular subtypes of urothelial carcinoma and gene signatures for molecular grading and outcome.

Description

In the present investigation, we sought to refine the classification of urothelial carcinoma by combining information on gene expression, genomic, and gene mutation levels. For these purposes, we performed gene expression analysis of 144 carcinomas, and whole genome array-CGH analysis and mutation analyses of FGFR3, PIK3CA, KRAS, HRAS, NRAS, TP53, CDKN2A, and TSC1 in 103 of these cases. Hierarchical cluster analysis identified two intrinsic molecular subtypes, MS1 and MS2, which were validated and defined by the same set of genes in three independent bladder cancer data sets. The two subtypes differed with respect to gene expression and mutation profiles, as well as with the level of genomic instability. The data show that genomic instability was the most distinguishing genomic feature of MS2 tumors, and that this trait was not dependent on TP53/MDM2 alterations. By combining molecular and pathologic data, it was possible to distinguish two molecular subtypes of T(a) and T(1) tumors, respectively. In addition, we define gene signatures validated in two independent data sets that classify urothelial carcinoma into low-grade (G(1)/G(2)) and high-grade (G(3)) tumors as well as non-muscle and muscle-invasive tumors with high precisions and sensitivities, suggesting molecular grading as a relevant complement to standard pathologic grading. We also present a gene expression signature with independent prognostic effect on metastasis and disease-specific survival. We conclude that the combination of molecular and histopathologic classification systems might provide a strong improvement for bladder cancer classification and produce new insights into the development of this tumor type.(c)2010 AACR.

Usage

data( GSE19915.GPL3883_eset )

Format

experimentData(eset):
Experiment data
  Experimenter name: Lindgren D, Frigyesi A, Gudjonsson S, Sj?dahl G et al. Combined gene expression and genomic profiling define two intrinsic molecular subtypes of urothelial carcinoma and gene signatures for molecular grading and outcome. Cancer Res 2010 May 1;70(9):3463-72 
  Laboratory: Lindgren,  H?glund 2010 
  Contact information:  
  Title: Combined gene expression and genomic profiling define two intrinsic molecular subtypes of urothelial carcinoma and gene signatures for molecular grading and outcome. 
  URL:  
  PMIDs: 20406976 

  Abstract: A 247 word abstract is available. Use 'abstract' method.
  Information is available on: preprocessing 
  notes:
   platform_title:     
      Swegene Human 27K RAP UniGene188 array
   platform_shorttitle:     
      Swegene Human 27K
   platform_summary:     
      
   platform_manufacturer:     
      other
   platform_distribution:     
      non-commercial
   platform_accession:     
      GPL3883
   platform_technology:     
      spotted DNA/cDNA

Preprocessing: default
featureData(eset):
An object of class 'AnnotatedDataFrame'
  featureNames: 13CDNA73 15E1.2 ... raptor|MGC14560 (10585 total)
  varLabels: probeset gene
  varMetadata: labelDescription

Details

assayData: 10585 features, 84 samples
Platform type: 
Overall survival time-to-event summary (in years):
Call: survfit(formula = Surv(time, cens) ~ -1)

   10 observations deleted due to missingness 
records   n.max n.start  events  median 0.95LCL 0.95UCL 
     74      74      74       4      NA      NA      NA 

--------------------------- 
Available sample meta-data: 
--------------------------- 

alt_sample_name: 
   Length     Class      Mode 
       84 character character 

sample_type: 
healthy   tumor 
      8      76 

summarystage: 
   invasive superficial        NA's 
          2          73           9 

T: 
   0    1    3 NA's 
  56   17    2    9 

G: 
   1    2    3 NA's 
  24   38   13    9 

days_to_death: 
   Min. 1st Qu.  Median    Mean 3rd Qu.    Max.    NA's 
      0    1231    1720    1552    1937    2429      10 

vital_status: 
deceased   living     NA's 
       4       70       10 

uncurated_author_metadata: 
   Length     Class      Mode 
       84 character character 


Combined gene expression and genomic profiling define two intrinsic molecular subtypes of urothelial carcinoma and gene signatures for molecular grading and outcome.

Description

In the present investigation, we sought to refine the classification of urothelial carcinoma by combining information on gene expression, genomic, and gene mutation levels. For these purposes, we performed gene expression analysis of 144 carcinomas, and whole genome array-CGH analysis and mutation analyses of FGFR3, PIK3CA, KRAS, HRAS, NRAS, TP53, CDKN2A, and TSC1 in 103 of these cases. Hierarchical cluster analysis identified two intrinsic molecular subtypes, MS1 and MS2, which were validated and defined by the same set of genes in three independent bladder cancer data sets. The two subtypes differed with respect to gene expression and mutation profiles, as well as with the level of genomic instability. The data show that genomic instability was the most distinguishing genomic feature of MS2 tumors, and that this trait was not dependent on TP53/MDM2 alterations. By combining molecular and pathologic data, it was possible to distinguish two molecular subtypes of T(a) and T(1) tumors, respectively. In addition, we define gene signatures validated in two independent data sets that classify urothelial carcinoma into low-grade (G(1)/G(2)) and high-grade (G(3)) tumors as well as non-muscle and muscle-invasive tumors with high precisions and sensitivities, suggesting molecular grading as a relevant complement to standard pathologic grading. We also present a gene expression signature with independent prognostic effect on metastasis and disease-specific survival. We conclude that the combination of molecular and histopathologic classification systems might provide a strong improvement for bladder cancer classification and produce new insights into the development of this tumor type.(c)2010 AACR.

Usage

data( GSE19915.GPL5186_eset )

Format

experimentData(eset):
Experiment data
  Experimenter name: Lindgren D, Frigyesi A, Gudjonsson S, Sj?dahl G et al. Combined gene expression and genomic profiling define two intrinsic molecular subtypes of urothelial carcinoma and gene signatures for molecular grading and outcome. Cancer Res 2010 May 1;70(9):3463-72 
  Laboratory: Lindgren,  H?glund 2010 
  Contact information:  
  Title: Combined gene expression and genomic profiling define two intrinsic molecular subtypes of urothelial carcinoma and gene signatures for molecular grading and outcome. 
  URL:  
  PMIDs: 20406976 

  Abstract: A 247 word abstract is available. Use 'abstract' method.
  Information is available on: preprocessing 
  notes:
   platform_title:     
      SWEGENE H_v3.0.1 35K
   platform_shorttitle:     
      SWEGENE H_v3.0.1 35K
   platform_summary:     
      
   platform_manufacturer:     
      other
   platform_distribution:     
      non-commercial
   platform_accession:     
      GPL5186
   platform_technology:     
      spotted oligonucleotide

Preprocessing: default
featureData(eset):
An object of class 'AnnotatedDataFrame'
  featureNames: 15E1_HUMAN 38596 ... ZZZ3 (12391 total)
  varLabels: probeset gene
  varMetadata: labelDescription

Details

assayData: 12391 features, 98 samples
Platform type: 
Overall survival time-to-event summary (in years):
Call: survfit(formula = Surv(time, cens) ~ -1)

   11 observations deleted due to missingness 
records   n.max n.start  events  median 0.95LCL 0.95UCL 
     87      87      87      26      NA      NA      NA 

--------------------------- 
Available sample meta-data: 
--------------------------- 

alt_sample_name: 
   Length     Class      Mode 
       98 character character 

sample_type: 
healthy   tumor 
      7      91 

summarystage: 
   invasive superficial        NA's 
         45          43          10 

T: 
   Min. 1st Qu.  Median    Mean 3rd Qu.    Max.    NA's 
  0.000   1.000   2.000   1.693   3.000   4.000      10 

G: 
   2    3 NA's 
  19   71    8 

days_to_death: 
   Min. 1st Qu.  Median    Mean 3rd Qu.    Max.    NA's 
    3.0   692.5  1117.0  1067.0  1512.0  2335.0      11 

vital_status: 
deceased   living     NA's 
      26       61       11 

uncurated_author_metadata: 
   Length     Class      Mode 
       98 character character 


A candidate molecular biomarker panel for the detection of bladder cancer.

Description

Bladder cancer is among the five most common malignancies worldwide, and due to high rates of recurrence, one of the most prevalent. Improvements in noninvasive urine-based assays to detect bladder cancer would benefit both patients and health care systems. In this study, the goal was to identify urothelial cell transcriptomic signatures associated with bladder cancer.Gene expression profiling (Affymetrix U133 Plus 2.0 arrays) was applied to exfoliated urothelia obtained from a cohort of 92 subjects with known bladder disease status. Computational analyses identified candidate biomarkers of bladder cancer and an optimal predictive model was derived. Selected targets from the profiling analyses were monitored in an independent cohort of 81 subjects using quantitative real-time PCR (RT-PCR).Transcriptome profiling data analysis identified 52 genes associated with bladder cancer (P ??? 0.001) and gene models that optimally predicted class label were derived. RT-PCR analysis of 48 selected targets in an independent cohort identified a 14-gene diagnostic signature that predicted the presence of bladder cancer with high accuracy.Exfoliated urothelia sampling provides a robust analyte for the evaluation of patients with suspected bladder cancer. The refinement and validation of the multigene urothelial cell signatures identified in this preliminary study may lead to accurate, noninvasive assays for the detection of bladder cancer.The development of an accurate, noninvasive bladder cancer detection assay would benefit both the patient and health care systems through better detection, monitoring, and control of disease.

Usage

data( GSE31189_eset )

Format

experimentData(eset):
Experiment data
  Experimenter name: Urquidi V, Goodison S, Cai Y, Sun Y et al. A candidate molecular biomarker panel for the detection of bladder cancer. Cancer Epidemiol Biomarkers Prev 2012 Dec;21(12):2149-58. 
  Laboratory: Urquidi, Rosser 2012 
  Contact information:  
  Title: A candidate molecular biomarker panel for the detection of bladder cancer. 
  URL:  
  PMIDs: 23097579 

  Abstract: A 230 word abstract is available. Use 'abstract' method.
  Information is available on: preprocessing 
  notes:
   platform_title:     
      [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array
   platform_shorttitle:     
      Affymetrix HG-U133Plus2
   platform_summary:     
      hgu133plus2
   platform_manufacturer:     
      Affymetrix
   platform_distribution:     
      commercial
   platform_accession:     
      GPL570
   platform_technology:     
      in situ oligonucleotide

Preprocessing: frma
featureData(eset):
An object of class 'AnnotatedDataFrame'
  featureNames: A1BG A1BG-AS1 ... ZZZ3 (19381 total)
  varLabels: probeset gene
  varMetadata: labelDescription

Details

assayData: 19381 features, 92 samples
Platform type: hgu133plus2
--------------------------- 
Available sample meta-data: 
--------------------------- 

alt_sample_name: 
   Length     Class      Mode 
       92 character character 

sample_type: 
healthy   tumor 
     40      52 

batch: 
   Length     Class      Mode 
       92 character character 

uncurated_author_metadata: 
   Length     Class      Mode 
       92 character character 


Combination of a novel gene expression signature with a clinical nomogram improves the prediction of survival in high-risk bladder cancer.

Description

We aimed to validate and improve prognostic signatures for high-risk urothelial carcinoma of the bladder.We evaluated microarray data from 93 patients with bladder cancer managed by radical cystectomy to determine gene expression patterns associated with clinical and prognostic variables. We compared our results with published bladder cancer microarray data sets comprising 578 additional patients and with 49 published gene signatures from multiple cancer types. Hierarchical clustering was utilized to identify subtypes associated with differences in survival. We then investigated whether the addition of survival-associated gene expression information to a validated postcystectomy nomogram utilizing clinical and pathologic variables improves prediction of recurrence.Multiple markers for muscle invasive disease with highly significant expression differences in multiple data sets were identified, such as fibronectin 1 (FN1), NNMT, POSTN, and SMAD6. We identified signatures associated with pathologic stage and the likelihood of developing metastasis and death from bladder cancer, as well as with two distinct clustering subtypes of bladder cancer. Our novel signature correlated with overall survival in multiple independent data sets, significantly improving the prediction concordance of standard staging in all data sets [mean ??C-statistic: 0.14; 95% confidence interval (CI), 0.01-0.27; P < 0.001]. Tested in our patient cohort, it significantly enhanced the performance of a postoperative survival nomogram (??C-statistic: 0.08, 95% CI, -0.04-0.20; P < 0.005).Prognostic information obtained from gene expression data can aid in posttreatment prediction of bladder cancer recurrence. Our findings require further validation in external cohorts and prospectively in a clinical trial setting.

Usage

data( GSE31684_eset )

Format

experimentData(eset):
Experiment data
  Experimenter name: Riester M, Taylor JM, Feifer A, Koppie T et al. Combination of a novel gene expression signature with a clinical nomogram improves the prediction of survival in high-risk bladder cancer. Clin Cancer Res 2012 Mar 1;18(5):1323-33.  
  Laboratory: Riester, Michor 2012 
  Contact information:  
  Title: Combination of a novel gene expression signature with a clinical nomogram improves the prediction of survival in high-risk bladder cancer. 
  URL:  
  PMIDs: 22228636 

  Abstract: A 243 word abstract is available. Use 'abstract' method.
  Information is available on: preprocessing 
  notes:
   platform_title:     
      [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array
   platform_shorttitle:     
      Affymetrix HG-U133Plus2
   platform_summary:     
      hgu133plus2
   platform_manufacturer:     
      Affymetrix
   platform_distribution:     
      commercial
   platform_accession:     
      GPL570
   platform_technology:     
      in situ oligonucleotide

Preprocessing: frma
featureData(eset):
An object of class 'AnnotatedDataFrame'
  featureNames: A1BG A1BG-AS1 ... ZZZ3 (19381 total)
  varLabels: probeset gene
  varMetadata: labelDescription

Details

assayData: 19381 features, 93 samples
Platform type: hgu133plus2
Overall survival time-to-event summary (in years):
Call: survfit(formula = Surv(time, cens) ~ -1)

records   n.max n.start  events  median 0.95LCL 0.95UCL 
  93.00   93.00   93.00   65.00    2.74    1.37    7.52 

--------------------------- 
Available sample meta-data: 
--------------------------- 

alt_sample_name: 
   Length     Class      Mode 
       93 character character 

sample_type: 
tumor 
   93 

surgery_type: 
rc 
93 

histological_type: 
     cis squamous      tcc 
       2        5       86 

summarygrade: 
high  low 
  87    6 

summarystage: 
   invasive superficial 
         78          15 

T: 
 0  1  2  3  4 
 5 10 17 42 19 

N: 
   0    1 NA's 
  49   28   16 

M: 
 0  1 
57 36 

age: 
   Min. 1st Qu.  Median    Mean 3rd Qu.    Max. 
  42.00   62.00   69.00   69.11   75.00   91.00 

gender: 
 f  m 
25 68 

neoadjuvant_chemo: 
 n  y 
90  3 

adjuvant_chemo: 
 n  y 
58 35 

days_to_tumor_recurrence: 
   Min. 1st Qu.  Median    Mean 3rd Qu.    Max. 
     12     170     495    1307    2574    5342 

recurrence_status: 
norecurrence   recurrence 
          54           39 

days_to_death: 
   Min. 1st Qu.  Median    Mean 3rd Qu.    Max. 
     12     299     953    1445    2616    5342 

vital_status: 
deceased   living 
      65       28 

dfs_event: 
doc dod ned 
 27  38  28 

smoking_status: 
current  former   never 
     19      56      18 

smoking_package_years: 
   Min. 1st Qu.  Median    Mean 3rd Qu.    Max.    NA's 
   5.00   22.50   40.00   44.13   60.00  120.00      22 

nomogram_score: 
   Min. 1st Qu.  Median    Mean 3rd Qu.    Max. 
   1.00   21.11   46.60   44.99   67.29   92.15 

batch: 
   Length     Class      Mode 
       93 character character 

uncurated_author_metadata: 
   Length     Class      Mode 
       93 character character 


A molecular taxonomy for urothelial carcinoma.

Description

Even though urothelial cancer is the fourth most common tumor type among males, progress in treatment has been scarce. A problem in day-to-day clinical practice is that precise assessment of individual tumors is still fairly uncertain; consequently efforts have been undertaken to complement tumor evaluation with molecular biomarkers. An extension of this approach would be to base tumor classification primarily on molecular features. Here, we present a molecular taxonomy for urothelial carcinoma based on integrated genomics.We use gene expression profiles from 308 tumor cases to define five major urothelial carcinoma subtypes: urobasal A, genomically unstable, urobasal B, squamous cell carcinoma like, and an infiltrated class of tumors. Tumor subtypes were validated in three independent publically available data sets. The expression of 11 key genes was validated at the protein level by immunohistochemistry.The subtypes show distinct clinical outcomes and differ with respect to expression of cell-cycle genes, receptor tyrosine kinases particularly FGFR3, ERBB2, and EGFR, cytokeratins, and cell adhesion genes, as well as with respect to FGFR3, PIK3CA, and TP53 mutation frequency. The molecular subtypes cut across pathologic classification, and class-defining gene signatures show coordinated expression irrespective of pathologic stage and grade, suggesting the molecular phenotypes as intrinsic properties of the tumors. Available data indicate that susceptibility to specific drugs is more likely to be associated with the molecular stratification than with pathologic classification.We anticipate that the molecular taxonomy will be useful in future clinical investigations.??2012 AACR.

Usage

data( GSE32894_eset )

Format

experimentData(eset):
Experiment data
  Experimenter name: Sj?dahl G, Lauss M, L?vgren K, Chebil G et al. A molecular taxonomy for urothelial carcinoma. Clin Cancer Res 2012 Jun 15;18(12):3377-86.  
  Laboratory: Sj?dahl,  H?glund 2012 
  Contact information:  
  Title: A molecular taxonomy for urothelial carcinoma. 
  URL:  
  PMIDs: 22553347 

  Abstract: A 236 word abstract is available. Use 'abstract' method.
  Information is available on: preprocessing 
  notes:
   platform_title:     
      Illumina HumanHT-12 V3.0 expression beadchip
   platform_shorttitle:     
      Illumina HumanHT-12 V3.0
   platform_summary:     
      illuminaHumanv3
   platform_manufacturer:     
      Illumina
   platform_distribution:     
      commercial
   platform_accession:     
      GPL6947
   platform_technology:     
      oligonucleotide beads

Preprocessing: default
featureData(eset):
An object of class 'AnnotatedDataFrame'
  featureNames: A1CF A2M ... ZZZ3 (15638 total)
  varLabels: probeset gene
  varMetadata: labelDescription

Details

assayData: 15638 features, 308 samples
Platform type: illuminaHumanv3
Overall survival time-to-event summary (in years):
Call: survfit(formula = Surv(time, cens) ~ -1)

   84 observations deleted due to missingness 
records   n.max n.start  events  median 0.95LCL 0.95UCL 
    224     224     224      25      NA      NA      NA 

--------------------------- 
Available sample meta-data: 
--------------------------- 

alt_sample_name: 
   Length     Class      Mode 
      308 character character 

sample_type: 
tumor 
  308 

summarystage: 
   invasive superficial        NA's 
         93         213           2 

T: 
   Min. 1st Qu.  Median    Mean 3rd Qu.    Max.    NA's 
 0.0000  0.0000  1.0000  0.9542  2.0000  4.0000       2 

G: 
   1    2    3    4 NA's 
  48  103  154    1    2 

N: 
   0    1    2    3 NA's 
  48    4   10    1  245 

age: 
   Min. 1st Qu.  Median    Mean 3rd Qu.    Max. 
  20.00   62.75   71.00   70.61   79.00   96.00 

gender: 
  f   m 
 80 228 

days_to_death: 
   Min. 1st Qu.  Median    Mean 3rd Qu.    Max.    NA's 
    6.0   552.5  1068.0  1214.0  1766.0  3357.0      84 

vital_status: 
deceased   living     NA's 
      25      199       84 

dfs_event: 
 dod NA's 
  25  283 

uncurated_author_metadata: 
   Length     Class      Mode 
      308 character character 


Transcriptional signatures of Ral GTPase are associated with aggressive clinicopathologic characteristics in human cancer.

Description

RalA and RalB are small GTPases that support malignant development and progression in experimental models of bladder, prostate, and squamous cancer. However, demonstration of their clinical relevance in human tumors remains lacking. Here, we developed tools to evaluate Ral protein expression, activation, and transcriptional output and evaluated their association with clinicopathologic parameters in common human tumor types. To evaluate the relevance of Ral activation and transcriptional output, we correlated RalA and RalB activation with the mutational status of key human bladder cancer genes. We also identified and evaluated a transcriptional signature of genes that correlates with depletion of RalA and RalB in vivo. The Ral transcriptional signature score, but not protein expression as evaluated by immunohistochemistry, predicted disease stage, progression to muscle invasion, and survival in human bladder cancers and metastatic and stem cell phenotypes in bladder cancer models. In prostate cancer, the Ral transcriptional signature score was associated with seminal vesicle invasion, androgen-independent progression, and reduced survival. In squamous cell carcinoma, this score was decreased in cancer tissues compared with normal mucosa, validating the experimental findings that Ral acts as a tumor suppressor in this tumor type. Together, our findings show the clinical relevance of Ral in human cancer and provide a rationale for the development of Ral-directed therapies.

Usage

data( GSE37317_eset )

Format

experimentData(eset):
Experiment data
  Experimenter name: Smith SC, Baras AS, Owens CR, Dancik G et al. Transcriptional signatures of Ral GTPase are associated with aggressive clinicopathologic characteristics in human cancer. Cancer Res 2012 Jul 15;72(14):3480-91.  
  Laboratory: Smith, Theodorescu 2012 
  Contact information:  
  Title: Transcriptional signatures of Ral GTPase are associated with aggressive clinicopathologic characteristics in human cancer. 
  URL:  
  PMIDs: 22586063 

  Abstract: A 210 word abstract is available. Use 'abstract' method.
  Information is available on: preprocessing 
  notes:
   platform_title:     
      [HG-U133A] Affymetrix Human Genome U133A Array
   platform_shorttitle:     
      Affymetrix HG-U133A
   platform_summary:     
      hgu133a
   platform_manufacturer:     
      Affymetrix
   platform_distribution:     
      commercial
   platform_accession:     
      GPL96
   platform_technology:     
      in situ oligonucleotide

Preprocessing: frma
featureData(eset):
An object of class 'AnnotatedDataFrame'
  featureNames: A1CF A2M ... ZZZ3 (13013 total)
  varLabels: probeset gene
  varMetadata: labelDescription

Details

assayData: 13013 features, 19 samples
Platform type: hgu133a
--------------------------- 
Available sample meta-data: 
--------------------------- 

alt_sample_name: 
   Length     Class      Mode 
       19 character character 

sample_type: 
tumor 
   19 

histological_type: 
squamous      tcc 
       1       18 

summarystage: 
   invasive superficial 
         11           8 

T: 
0 1 2 3 4 
4 4 4 3 4 

batch: 
   Length     Class      Mode 
       19 character character 

uncurated_author_metadata: 
   Length     Class      Mode 
       19 character character 


Emmprin and survivin predict response and survival following cisplatin-containing chemotherapy in patients with advanced bladder cancer.

Description

Cisplatin-containing chemotherapy is the standard of care for patients with locally advanced and metastatic transitional cell carcinoma of the urothelium. The response rate is approximately 50% and tumor-derived molecular prognostic markers are desirable for improved estimation of response and survival.Affymetrix GeneChip expression profiling was carried out using tumor material from 30 patients. A set of genes with an expression highly correlated to survival time after chemotherapy was identified. Two genes were selected for validation by immunohistochemistry in an independent material of 124 patients receiving cisplatin-containing therapy.Fifty-five differentially expressed genes correlated significantly to survival time. Two of the protein products (emmprin and survivin) were validated using immunohistochemistry. Multivariate analysis identified emmprin expression (hazard ratio, 2.23; P < 0.0001) and survivin expression (hazard ratio, 2.46; P < 0.0001) as independent prognostic markers for poor outcome, together with the presence of visceral metastases (hazard ratio, 2.62; P < 0.0001). In the clinical good prognostic group of patients without visceral metastases, both markers showed significant discriminating power as supplemental risk factors (P < 0.0001). Within this group of patients, the subgroups of patients with no positive, one positive, or two positive immunohistochemistry scores (emmprin and survivin) had estimated 5-year survival rates of 44.0%, 21.1%, and 0%, respectively. Response to chemotherapy could also be predicted with an odds ratio of 4.41 (95% confidence interval, 1.91-10.1) and 2.48 (95% confidence interval, 1.1-5.5) for emmprin and survivin, respectively.Emmprin and survivin proteins were identified as strong independent prognostic factors for response and survival after cisplatin-containing chemotherapy in patients with advanced bladder cancer.

Usage

data( GSE5287_eset )

Format

experimentData(eset):
Experiment data
  Experimenter name: Als AB, Dyrskj?t L, von der Maase H, Koed K et al. Emmprin and survivin predict response and survival following cisplatin-containing chemotherapy in patients with advanced bladder cancer. Clin Cancer Res 2007 Aug 1;13(15 Pt 1):4407-14. 
  Laboratory: Als, Orntoft 2007 
  Contact information:  
  Title: Emmprin and survivin predict response and survival following cisplatin-containing chemotherapy in patients with advanced bladder cancer. 
  URL:  
  PMIDs: 17671123 

  Abstract: A 254 word abstract is available. Use 'abstract' method.
  Information is available on: preprocessing 
  notes:
   platform_title:     
      [HG-U133A] Affymetrix Human Genome U133A Array
   platform_shorttitle:     
      Affymetrix HG-U133A
   platform_summary:     
      hgu133a
   platform_manufacturer:     
      Affymetrix
   platform_distribution:     
      commercial
   platform_accession:     
      GPL96
   platform_technology:     
      in situ oligonucleotide

Preprocessing: frma
featureData(eset):
An object of class 'AnnotatedDataFrame'
  featureNames: A1CF A2M ... ZZZ3 (13013 total)
  varLabels: probeset gene
  varMetadata: labelDescription

Details

assayData: 13013 features, 30 samples
Platform type: hgu133a
Overall survival time-to-event summary (in years):
Call: survfit(formula = Surv(time, cens) ~ -1)

records   n.max n.start  events  median 0.95LCL 0.95UCL 
  30.00   30.00   30.00   25.00    4.36    3.12    7.81 

--------------------------- 
Available sample meta-data: 
--------------------------- 

alt_sample_name: 
   Length     Class      Mode 
       30 character character 

sample_type: 
tumor 
   30 

summarystage: 
invasive 
      30 

T: 
 4 
30 

neoadjuvant_chemo: 
 n 
30 

adjuvant_chemo: 
 y 
30 

adjuvant_regimen: 
cisplatin 
       30 

days_to_death: 
   Min. 1st Qu.  Median    Mean 3rd Qu.    Max. 
    420    1080    1590    3160    2962   12600 

vital_status: 
deceased   living 
      25        5 

batch: 
   Length     Class      Mode 
       30 character character 

uncurated_author_metadata: 
   Length     Class      Mode 
       30 character character 


Identifying distinct classes of bladder carcinoma using microarrays.

Description

Bladder cancer is a common malignant disease characterized by frequent recurrences. The stage of disease at diagnosis and the presence of surrounding carcinoma in situ are important in determining the disease course of an affected individual. Despite considerable effort, no accepted immunohistological or molecular markers have been identified to define clinically relevant subsets of bladder cancer. Here we report the identification of clinically relevant subclasses of bladder carcinoma using expression microarray analysis of 40 well characterized bladder tumors. Hierarchical cluster analysis identified three major stages, Ta, T1 and T2-4, with the Ta tumors further classified into subgroups. We built a 32-gene molecular classifier using a cross-validation approach that was able to classify benign and muscle-invasive tumors with close correlation to pathological staging in an independent test set of 68 tumors. The classifier provided new predictive information on disease progression in Ta tumors compared with conventional staging (P < 0.005). To delineate non-recurring Ta tumors from frequently recurring Ta tumors, we analyzed expression patterns in 31 tumors by applying a supervised learning classification methodology, which classified 75% of the samples correctly (P < 0.006). Furthermore, gene expression profiles characterizing each stage and subtype identified their biological properties, producing new potential targets for therapy.

Usage

data( GSE89_eset )

Format

experimentData(eset):
Experiment data
  Experimenter name: Dyrskj?t L, Thykjaer T, Kruh?ffer M, Jensen JL et al. Identifying distinct classes of bladder carcinoma using microarrays. Nat Genet 2003 Jan;33(1):90-6.  
  Laboratory: Dyrskjot, Orntoft 2003 
  Contact information:  
  Title: Identifying distinct classes of bladder carcinoma using microarrays. 
  URL:  
  PMIDs: 12469123 

  Abstract: A 202 word abstract is available. Use 'abstract' method.
  Information is available on: preprocessing 
  notes:
   platform_title:     
      [Hu6800] Affymetrix Human Full Length HuGeneFL Array
   platform_shorttitle:     
      Affymetrix HuGeneFL
   platform_summary:     
      hu6800
   platform_manufacturer:     
      Affymetrix
   platform_distribution:     
      commercial
   platform_accession:     
      GPL80
   platform_technology:     
      in situ oligonucleotide

Preprocessing: rma
featureData(eset):
An object of class 'AnnotatedDataFrame'
  featureNames: A2M AADAC ... ZYX (5466 total)
  varLabels: probeset gene
  varMetadata: labelDescription

Details

assayData: 5466 features, 40 samples
Platform type: hu6800
--------------------------- 
Available sample meta-data: 
--------------------------- 

alt_sample_name: 
   Length     Class      Mode 
       40 character character 

sample_type: 
tumor 
   40 

summarystage: 
   invasive superficial 
          9          31 

T: 
 0  1  2 
20 11  9 

G: 
   2    3    4 NA's 
   6   32    1    1 

uncurated_author_metadata: 
   Length     Class      Mode 
       40 character character 


Regional copy number-independent deregulation of transcription in cancer.

Description

Genetic and epigenetic alterations have been identified that lead to transcriptional deregulation in cancers. Genetic mechanisms may affect single genes or regions containing several neighboring genes, as has been shown for DNA copy number changes. It was recently reported that epigenetic suppression of gene expression can also extend to a whole region; this is known as long-range epigenetic silencing. Various techniques are available for identifying regional genetic alterations, but no large-scale analysis has yet been carried out to obtain an overview of regional epigenetic alterations. We carried out an exhaustive search for regions susceptible to such mechanisms using a combination of transcriptome correlation map analysis and array CGH data for a series of bladder carcinomas. We validated one candidate region experimentally, demonstrating histone methylation leading to the loss of expression of neighboring genes without DNA methylation.

Usage

data( PMID17099711.GPL8300_eset )

Format

experimentData(eset):
Experiment data
  Experimenter name: Stransky N, Vallot C, Reyal F, Bernard-Pierrot I, de Medina SG, Segraves R, de Rycke Y, Elvin P, Cassidy A, Spraggon C, Graham A, Southgate J, Asselain B, Allory Y, Abbou CC, Albertson DG, Thiery JP, Chopin DK, Pinkel D, Radvanyi F. Regional copy number-independent deregulation of transcription in cancer. Nat Genet. 2006 Dec;38(12):1386-96. Epub 2006 Nov 12. 
  Laboratory: Stransky, Radvany 2006 
  Contact information:  
  Title: Regional copy number-independent deregulation of transcription in cancer. 
  URL:  
  PMIDs: 17099711 

  Abstract: A 136 word abstract is available. Use 'abstract' method.
  Information is available on: preprocessing 
  notes:
   platform_title:     
      [HG_U95Av2] Affymetrix Human Genome U95 Version 2 Array
   platform_shorttitle:     
      Affymetrix U95Av2
   platform_summary:     
      hgu95av2
   platform_manufacturer:     
      Affymetrix
   platform_distribution:     
      commercial
   platform_accession:     
      GPL8300
   platform_technology:     
      NA

Preprocessing: rma
featureData(eset):
An object of class 'AnnotatedDataFrame'
  featureNames: AADAC AAK1 ... ZZZ3 (8950 total)
  varLabels: probeset gene
  varMetadata: labelDescription

Details

assayData: 8950 features, 30 samples
Platform type: hgu95av2
--------------------------- 
Available sample meta-data: 
--------------------------- 

unique_patient_ID: 
   Length     Class      Mode 
       30 character character 

sample_type: 
tumor 
   30 

summarystage: 
   invasive superficial 
         14          16 

T: 
 0  1  2  3  4 
10  6  1  5  8 

substage: 
   a    b NA's 
  13    6   11 

G: 
 1  2  3 
 8  5 17 

N: 
   0    1    2 NA's 
  18    3    5    4 

M: 
   0 NA's 
  26    4 

gender: 
 f  m 
 5 25 

batch: 
2002-01-23 2002-01-24 2002-09-20 2003-03-06 
         6          3         14          7 

uncurated_author_metadata: 
   Length     Class      Mode 
       30 character character 


Regional copy number-independent deregulation of transcription in cancer.

Description

Genetic and epigenetic alterations have been identified that lead to transcriptional deregulation in cancers. Genetic mechanisms may affect single genes or regions containing several neighboring genes, as has been shown for DNA copy number changes. It was recently reported that epigenetic suppression of gene expression can also extend to a whole region; this is known as long-range epigenetic silencing. Various techniques are available for identifying regional genetic alterations, but no large-scale analysis has yet been carried out to obtain an overview of regional epigenetic alterations. We carried out an exhaustive search for regions susceptible to such mechanisms using a combination of transcriptome correlation map analysis and array CGH data for a series of bladder carcinomas. We validated one candidate region experimentally, demonstrating histone methylation leading to the loss of expression of neighboring genes without DNA methylation.

Usage

data( PMID17099711.GPL91_eset )

Format

experimentData(eset):
Experiment data
  Experimenter name: Stransky N, Vallot C, Reyal F, Bernard-Pierrot I, de Medina SG, Segraves R, de Rycke Y, Elvin P, Cassidy A, Spraggon C, Graham A, Southgate J, Asselain B, Allory Y, Abbou CC, Albertson DG, Thiery JP, Chopin DK, Pinkel D, Radvanyi F. Regional copy number-independent deregulation of transcription in cancer. Nat Genet. 2006 Dec;38(12):1386-96. Epub 2006 Nov 12. 
  Laboratory: Stransky, Radvany 2006 
  Contact information:  
  Title: Regional copy number-independent deregulation of transcription in cancer. 
  URL:  
  PMIDs: 17099711 

  Abstract: A 136 word abstract is available. Use 'abstract' method.
  Information is available on: preprocessing 
  notes:
   platform_title:     
      [HG_U95A] Affymetrix Human Genome U95A Array
   platform_shorttitle:     
      Affymetrix U95A
   platform_summary:     
      hgu95a
   platform_manufacturer:     
      Affymetrix
   platform_distribution:     
      commercial
   platform_accession:     
      GPL91
   platform_technology:     
      NA

Preprocessing: rma
featureData(eset):
An object of class 'AnnotatedDataFrame'
  featureNames: AADAC AAK1 ... ZZZ3 (8948 total)
  varLabels: probeset gene
  varMetadata: labelDescription

Details

assayData: 8948 features, 31 samples
Platform type: hgu95a
--------------------------- 
Available sample meta-data: 
--------------------------- 

unique_patient_ID: 
   Length     Class      Mode 
       31 character character 

sample_type: 
healthy   tumor 
      5      26 

summarystage: 
   invasive superficial        NA's 
         17           9           5 

T: 
   Min. 1st Qu.  Median    Mean 3rd Qu.    Max.    NA's 
  0.000   1.000   2.000   2.077   3.000   4.000       5 

substage: 
   a    b NA's 
  11    4   16 

G: 
   1    2    3 NA's 
   4    7   15    5 

N: 
   0    1    2 NA's 
  20    1    2    8 

M: 
   0    1 NA's 
  20    2    9 

gender: 
 f  m 
 7 24 

batch: 
   Length     Class      Mode 
       31 character character 

uncurated_author_metadata: 
   Length     Class      Mode 
       31 character character 


Clinically Annotated Data for the Bladder Cancer Transcriptome

Description

The curatedBladderData package provides manually curated clinical data, uniformly processed expression data, and convenience functions for gene expression analysis in patients with ovarian cancer.

Details

Package: curatedBladderData
Type: Package
Version: 1.48.0
Date: 2019-03-28
License: Artistic-2.0
Depends: R (>= 2.10.0), affy

Author(s)

Benjamin F. Ganzfried, Steve Skates, Markus Riester, Victoria Wang, Thomas Risch, Benjamin Haibe-Kains, Curtis Huttenhower, Svitlana Tyekucheva, Jie Ding, Ina Jazic, Michael Birrer, Giovanni Parmigiani, Levi Waldron

Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Harvard School of Public Health

Maintainer: Levi Waldron <[email protected]>

Examples

##List all datasets:
data(package="curatedBladderData")
##