Transcription profiling of human bladder tumours to construct a tumour stage classifier
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
DISEASE(S): tumor stage T2+
SUBMITTER: Lars Dyrskjøt Andersen
PROVIDER: E-GEOD-89 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Publications
Identifying distinct classes of bladder carcinoma using microarrays.
Dyrskjøt Lars L Thykjaer Thomas T Kruhøffer Mogens M Jensen Jens Ledet JL Marcussen Niels N Hamilton-Dutoit Stephen S Wolf Hans H Orntoft Torben F TF
Nature genetics 20021209 1
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 exp ...[more]
Similar Datasets
Project description:While aberrant protein glycosylation is a recognised characteristic of human cancers, advances in glycoanalytics continue to discover new associations between glycoproteins and tumourigenesis. This glycomics-centric study investigates a possible link between protein paucimannosylation, an under-studied class of human N-glycosylation [Man1-3GlcNAc2Fuc0-1] and human cancers. The distribution of paucimannosidic glycans (PMGs) within the N-glycome of 34 cancer cell lines and 133 tissue samples spanning 11 prevalent cancer types and matching non-cancerous specimens were accurately determined from 467 PGC-LC-MS/MS datasets collected over a decade within our laboratories. PMGs, particularly the α1,6-fucosylated bi- and tri-mannosylated N-glycans, were prominent features of 29 cancer cell lines, but the PMG level varied dramatically across and within the investigated cancer types (1.0%-50.2%). Analyses of paired (tumour/non-tumour) and stage-stratified tissue cohorts demonstrated that PMGs are significantly enriched in tumours from four cancer types including liver and colorectal cancer and increase with prostate cancer and chronic lymphocytic leukaemia progression. Cancer cell surface expression of paucimannosidic proteins was demonstrated using immunofluorescence while biosynthetic involvement of β-hexosaminidase was indicated by quantitative proteomics. The intriguing association between protein paucimannosylation and human cancers reported here warrants further exploration to detail the biosynthesis, cellular location(s), protein carriers and functions of paucimannosylation in tumourigenesis and metastasis.
2021-03-07 | PXD014271 | Pride
Project description:In a transcriptome study of psoriatic (PP) vs. normal (NN) skin, we found a co-expressed gene module (N5) enriched 11.5-fold for lipid biosynthetic genes. We also observed fewer visible hairs in PP skin, compared to uninvolved (PN) or NN skin (p<0.0001). To ask whether these findings might be due to abnormalities of the pilosebaceous unit, we carried out 3D morphometric analysis of paired PP and PN biopsies. Sebaceous glands (SG) were markedly atrophic in PP vs. PN skin (91% average reduction in volume, p=0.031). Module N5 genes were strongly downregulated in PP vs. NN skin (fold-change [FC] < 0.25, 44.4-fold), and strongly up-regulated in sebaceous hyperplasia (SH, FC > 4, 54.1-fold). The intersection of PP-downregulated and SH-upregulated gene lists generated a gene expression signature consisting solely of module N5 genes, whose expression in PP vs. NN skin was inversely correlated with the signature of IL17-stimuated keratinocytes. Despite loss of visible hairs, morphometry identified elongated follicles in PP vs. PN skin (average 1.7 vs. 1.2 Jm, p=0.020). These results document SG atrophy in non-scalp psoriasis, identify a cytokine-regulated set of SG signature genes, and suggest that loss of visible hair in PP skin may result from abnormal SG function. Gene expression was compared between sebaceous hyperplasia lesions (n = 5) and normal skin (n = 3) from control subjects.
2016-06-02 | E-GEOD-82140 | biostudies-arrayexpress
Project description:Background: Previous array CGH analyses have revealed several recurring genomic alterations in urothelial carcinoma. The most common genomic amplifications occur at 6p22 and 1q21-24. The main target gene at 6p22 is believed to be E2F3. This gene is frequently co-amplified with CDKAL1 and SOX4 and there are reports on 6p22 amplifications that do not include the E2F3 locus. Previous array CGH analyses have indicated multiple possible target regions at 1q21-24. However, due to complex rearrangements it has been difficult to identify specific 1q21-24 target regions and target genes. Results: We show that the most commonly amplified gene at 6p22 is SOX4 and that SOX4 can be amplified and over expressed without E2F3 or CDKAL1 being included in the amplicon. Hence, our data point to SOX4 as an auxiliary amplification target at 6p22. We further show that at least three amplified regions are observed at 1q21-24. Copy number data, combined with gene expression data, highlighted BCL9 and CHD1L as possible targets in the most proximal region and MCL1, SETDB1, and HIF1B as targets in the middle region, whereas no obvious gene targets could be determined in the most distal amplicon. We also highlight the enrichment of G4 quadruplex sequence motifs and the high number of intraregional sequence duplications, both known to contribute to genomic instability, as prominent features of the 1q21-24 region. Conclusions: Our detailed analyses of the 6p22 amplicon in urothelial carcinomas suggest SOX4 as an auxiliary target gene for amplification. We further demonstrate three separate target regions for amplification at 1q21-24 and identified BCL9, CHD1L, MCL1, SETDB1, and HIF1B as likely target genes within these regions. The study was conducted on genomic DNA from 68 primary fresh-frozen urothelial carcinoma tumors analysed using a Agilent SurePrint G3 4x180k Custom CGH Microarray Platform (028432). Samples were selected based on the presence of copy number alterations observed on lower resolution genomic data (32K BAC array). The majority of the BAC data is publicly available in GEO submissions GSE32535 and GSE19915. CN profiles for a minority of samples were derived from Illumina Methylation27k arrays according to Lauss et al 2012 [PMID: 22705924] and can be recreated from the data deposited in GSE33510 (derived CN data). Sample names are the same between all studies. This dataset also partly overlaps with Series GSE32894 (gene expression data). Names of the overlapping sample names are the same and indicated in the description field. Data from GSE32894 was used to calculate correlations between CN and gene expression.
2013-08-30 | E-GEOD-40938 | biostudies-arrayexpress
Project description:The objective of this study was to determine whether prostate cancer-associated miRNAs are present in seminal fluid and, if so, evaluate their diagnostic potential. Small RNA sequencing was used to profile and compare miRNAs in the non-sperm cellular fraction of seminal fluid from men with biopsy-proven cancer (one pooled sample from 6 men) and men with elevated serum PSA but negative biopsy results (one pooled sample from 6 men).
2014-04-15 | E-GEOD-56686 | biostudies-arrayexpress
Project description:Patient-control group project investigating recurrent failure of embryo-implantation by expression analysis of endometrium biopsies
2015-12-31 | E-MTAB-2591 | biostudies-arrayexpress
Project description:We assessed DNA methylation and copy number status of 27,000 CpGs in 149 urothelial carcinomas and integrated the findings with gene expression and mutation data. Methylation was associated with gene expression for 1,332 CpGs, of which 26% showed positive correlation with expression, i.e., high methylation and high gene expression levels. These positively correlated CpGs were part of specific transcription factor binding sites, such as sites for MYC and CREBP1, or located in gene bodies. Furthermore, we found genes with copy number gains, low expression and high methylation levels, revealing an association between methylation and copy number levels. This phenomenon was typically observed for developmental genes, such as HOX genes and tumor suppressor genes. In contrast, we also identified genes with copy number gains, high expression and low methylation levels. This was for instance observed for some keratin genes. Tumor cases could be grouped into four subgroups, termed epitypes, by their DNA methylation profiles. One epitype was influenced by the presence of infiltrating immune cells, two epitypes were mainly composed of non-muscle invasive tumors, and the remaining epitype of muscle invasive tumors. The polycomb complex protein EZH2 that blocks differentiation in embryonic stem cells showed increased expression both at the mRNA and protein levels in the muscle invasive epitype, together with methylation of polycomb target genes and HOX genes. Our data highlights HOX gene silencing and EZH2 expression as mechanisms to promote a more undifferentiated and aggressive state in UC. The study was conducted on genomic DNA from 150 primary fresh-frozen urothelial carcinoma tumors selected to have equal representation of stages Ta, T1 and T2>. The design also included four fully methylated and four unmethylated hybridization controls as well as 7 Normal urothelium samples. One tumor sample (UC_0556_1) was included as a technical replicate in each of four bisulfite treatment batches. The samples were bisulfite treated and hybridized to Illumina Human Methylation27 Bead Chip arrays according to manufacturers instructions at the SCIBLU Genomics Centre at Lund University, Sweden. Note: Illumina methylation data set comprises total of 168 samples (raw data), but 156 samples (processed data), derived from primary urothelial carcinoma samples. See README.txt for details of the 12 samples not included in the final, processed data.
2012-08-31 | E-GEOD-33510 | biostudies-arrayexpress
Project description:BACKGROUND: Broccoli consumption has been associated with a reduction in risk of prostate cancer. Isothiocyanates (ITC) derived from glucosinolates that accumulate in broccoli are potential dietary compounds that may mediate these health effects. Sulforaphane (SF, 4-methylsulphinylbutyl ITC) accumulates in heading broccoli (calabrese) and iberin (IB, 3-methylsulphinypropyl ITC) accumulates in sprouting broccoli. While, there are many studies regarding the biological activity of SF, there are few studies associated with IB. Moreover, the majority of studies have been undertaken with transformed cells, usually epithelial in origin, that have cancerous phenotypes. <br>METHOD: Primary epithelial and stromal cells were derived from benign prostatic hyperplasia tissue. Affymetrix U133 Plus 2.0 whole genome arrays were used to quantify global gene expression changes in these cells, following exposure to physiologically appropriate concentrations of SF and IB. Ontology and pathway analyses were used to interpret results. Changes in expression of a subset of genes were confirmed by RT PCR.<br>RESULTS: Global gene expression profiling identified epithelial and stromal specific gene expression profiles. IB and SF induced different changes in gene expression in both epithelial and stromal cells but these changes were associated with similar functions<br>CONCLUSION: This data suggests that IB and SF both induce genes associated with cancer prevention, and IB should be further investigated as a potential chemo-preventative target. <br>
2009-06-05 | E-MEXP-2034 | biostudies-arrayexpress
Project description:Genomic and gene expression profiling identifies two major gene/genomic circuits operating in urothelial carcinoma 131 primary bladder cancer tumor samples were analyzed on Illumina gene expression Bead Arrays.
2012-06-17 | E-GEOD-32548 | biostudies-arrayexpress
Project description:The aims of the study were investigated whether expression of urinary cell-free miRNAs would be different between prostate cancer (CaP) patients and non-cancer subjects with benign prostatic hyperplasia (BPH). Urinary cell-free miRNAs will provide potential benefits for detecting CaP, and virus-encoded hsv1-miR-H18 and hsv2-miR-H9-5p could be the important urinary diagnostic markers of CaP. It would be interesting because this is the first report about virus-encoded miRNAs related to CaP, and two miRNAs showed good diagnostic performance even in patients with PSA gray zone. A total 14 urines from patients with CaP (7 localized and 7 advanced stage) and 5 of BPH controls were used for miRNA array analysis.
2014-01-14 | E-GEOD-54010 | biostudies-arrayexpress
Project description:Background: With the incidence of papillary thyroid carcinoma rising worldwide, the decision about lobectomy versus total thyroidectomy will become relevant for an increasing number of patients. There exists no reliable biomarker for metastatic potential or tendency of recurrence that could assist in the risk stratification of patients. Objective: To develop a gene expression classifier for metastatic potential by measuring RNA expression in the primary tumor at the time of cancer surgery. Further, to investigate the ability of the gene expression classifier to identify metastatic and recurrent cases. Method: Genome-wide expression analyses. The development cohort consisted of freshly frozen tissues from 38 patients collected between the years 1986 and 2009. Validation was performed on a consecutive cohort of formalin fixated paraffin embedded surgical tissue specimens from 183 patients treated at Odense and Aarhus University Hospitals. Results: A 17 gene classifier (ADAMTS1, ANTXR1, C7, CXCL12, EBF1, FBLN2, FOSL2, GGT5, GPR124, JAM3, LRIG1, NDRG1, PRRX1, ROBO1, SORL1, TCF4, and ZEB1) was identified based on the expression values of these genes in the groups with and without metastasis in the development cohort. The 17 gene classifier for regional and/or distant metastasis identified was tested against the clinical status in the validation cohort. Sensitivity was 51.6% (95% CI 41.2%-61.8) and specificity 61.6 % (95% CI 50.5%-71.9%). Further, the Kaplan-Meyer method was used to estimate whether the classifier was useful as a prognostic marker for recurrences. Log-rank testing failed to identify any significance (p=0.32). Conclusion: A 17 gene classifier for metastatic potential was developed, and the results showed a clear biological difference between groups. However, through validation, the prognostic significance of this classifier could not be shown in identifying metastatic cases or in the ability of dichotomizing patients according to risk of recurrence after primary treatment. 38 patients with papillary thyroid carcinoma from a consecutive cohort of patients, no replicates
2015-01-20 | E-GEOD-65074 | biostudies-arrayexpress