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GSE11001
Homo sapiens
30 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The routine workflow for invasive cancer diagnostics is based on biopsy processing by formalin fixation and subsequent paraffin embedding. Formalin-fixed paraffin-embedded (FFPE) tissue samples are easy to handle, stable and particularly suitable for morphologic evaluation, immunohistochemistry and in situ hybridization. However, it has become a paradigm that these samples cannot be used for genome-wide expression analysis with microarrays. To oppose this view, we present a pilot microarray study using FFPE core needle biopsies from breast cancers as RNA source. We found that microarray probes interrogating sequences near the poly-A-tail of the transcribed genes were well suitable to measure RNA levels in FFPE core needle biopsies. For the ER and the HER2 gene, we observed strong correlations between RNA levels measured in these probe sets and protein expression determined by immunohistochemistry (p = 0.000003 and p = 0.0022). Further, we have identified a signature of 364 genes that correlated with ER protein status and a signature of 528 genes that correlated with HER2 protein status. Many of these genes (ER: 60%) could be confirmed by analysis of an independent publicly available data set. Finally, a hierarchical clustering of the biopsies with respect to three recently reported gene expression grade signatures resulted in widely stable low and high expression grade clusters that correlated with the pathological tumor grade. These findings support the notion that clinically relevant information can be gained from microarray based gene expression profiling of FFPE cancer biopsies. This opens new opportunities for the integration of gene expression analysis into the workflow of invasive cancer diagnostics as well as translational research in the setting of clinical studies.
Publication Title
Genome-wide gene expression profiling of formalin-fixed paraffin-embedded breast cancer core biopsies using microarrays.
Sample Metadata Fields
Disease stage
View Samples- Mus musculus
- 98 Downloadable Samples
Illumina HiSeq 2000
Description
Acinar cells make up the majority of all cells in the pancreas, yet the source of new acinar cells during homeostasis remains unknown. Using multicolor lineage-tracing and organoid-formation assays, we identified the presence of a progenitor-like acinar cell subpopulation. These cells have long-term self-renewal capacity, albeit in a unipotent fashion. We further demonstrate that binuclear acinar cells are terminally differentiated acinar cells. Transcriptome analysis of single acinar cells revealed the existence of a minor population of cells expressing progenitor markers. Interestingly, a gain of the identified markers accompanied by a transient gain of proliferation was observed following chemically induced pancreatitis. Altogether, our study identifies a functionally and molecularly distinct acinar subpopulation and thus transforms our understanding of the acinar cell compartment as a pool of equipotent secretory cells. Overall design: The single-cell RNA-seq library preparation protocol was based on the SMART seq2 protocol (Picelli et al., 2014) with following modifications. Acinar cells were isolated as described in the section Acinar Cell Isolation and Culture and resuspended in DPBS without Ca2+ and Mg2+ (PAN-Biotech). Cells were collected in a volume of 0.5 µL and transferred to a reaction tube containing 4 µL of 6 M guanidine-HCl (Sigma-Aldrich), 0.1% (v/v) Triton X-100 (Sigma-Aldrich) and 1% (v/v) 2-mercaptoethanol (?Sigma-Aldrich). The tube was immediately transferred into liquid nitrogen and kept there for the duration of cell collection. Next, 2.2× RNA SPRI beads (Beckman Coulter) were added directly to the lysis buffer and incubated for 5 min at room temperature. The beads were washed twice with 70% ethanol. Air-dried beads were resuspended in a solution containing 2 µL of H20, 1 µL of oligo(dT) primer, and 1 µL of dNTP Mix (primer and nucleotides used as in Picelli et al., 2014). Twenty-four cells contained ERCC Spike-In RNAs (1:10,000; Mix2, Ambion) Mix in addition to primer and nucleotides. Beads were incubated for 3 min at 72°C, and reverse transcription and PCR (19 cycles) were performed as described by Picelli et al. (2014). PCR product was cleaned up using 0.8× DNA SPRI beads (Beckman Coulter), and air-dried beads were resuspended in 15 µL of H2O. The quality of cDNA library was assessed for each cell on a high-sensitivity DNA Bioanalyzer chip. Subsequent steps (tagmentation, amplification, multiplexing) were done as previously described (Llorens-Bobadilla et al., 2015). The DKFZ Genomics and Proteomics Core Facility conducted sequencing on an Illumina HiSeq2000 sequencer (paired-end 100 bp).
Publication Title
Single-Cell Analysis Uncovers Clonal Acinar Cell Heterogeneity in the Adult Pancreas.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Rattus norvegicus
- 6 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
The MUC1 oncoprotein is aberrantly overexpressed in diverse human malignancies including breast and lung cancer. Although MUC1 modulates the activity of several transcription factors, there is no information regarding the effects of MUC1 on global gene expression patterns and the potential role of MUC1-induced genes in predicting outcome for cancer patients. We have developed an experimental model of MUC1-induced transformation that has identified the activation of gene families involved in oncogenesis, angiogenesis and extracellular matrix remodeling. A set of experimentally-derived MUC1-induced genes associated with tumorigenesis was applied to the analysis of breast and lung adenocarcinoma cancer databases. A 35-gene MUC1-induced tumorigenesis signature (MTS) predicts significant decreases in both disease-free and overall survival in patients with breast (n = 295) and lung (n = 442) cancers. The data demonstrate that the MUC1 oncoprotein contributes to the regulation of genes that are highly predictive of clinical outcome in breast and lung cancer patients.
Publication Title
MUC1-induced alterations in a lipid metabolic gene network predict response of human breast cancers to tamoxifen treatment.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Gastric cancer is one of the most common causes of cancer-related deaths worldwide. The lymph node status represents the strongest prognostic factor. Due to its extremely poor prognosis, the identification of novel therapeutic targets is urgently needed. Therefore, we aimed to assess differentially expressed genes in nodal negative versus nodal positive intestinal type gastric carcinoma by GeneChip array technique. The transcriptional profile of 6 gastric cancers with and without lymphatic dissemination was analyzed. A total of 115 transcripts were found to be up- and 219 to be down-regulated in node positive compared with node negative gastric cancers. Next we searched for differentially expressed GPCRs. We identified 52 GPCRs and GPCR-related genes, which were up- or down-regulated with a fold change factor greater 1.5.
Publication Title
Vascular CXCR4 expression - a novel antiangiogenic target in gastric cancer?
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 80 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Ovarian carcinoma has the highest mortality rate among gynecological malignancies. In this project, we investigated the hypothesis that molecular markers are able to predict outcome of ovarian cancer independently of classical clinical predictors, and that these molecular markers can be validated using independent data sets. We applied a semi-supervised method for prediction of patient survival. Microarrays from a cohort of 80 ovarian carcinomas (TOC cohort) were used for the development of a predictive model, which was then evaluated in an entirely independent cohort of 118 carcinomas (Duke cohort). A 300 gene ovarian prognostic index (OPI) was generated and validated in a leave-one-out approach in the TOC cohort (Kaplan-Meier analysis, p=0.0087). In a second validation step the prognostic power of the OPI was confirmed in an independent data set (Duke cohort, p=0.0063). In multivariate analysis, the OPI was independent of the postoperative residual tumour, the main clinico-pathological prognostic parameter with an adjusted hazard ratio of 6.4 (TOC cohort, CI 1.8 23.5, p=0.0049) and 1.9 (Duke cohort, CI 1.2 3.0, p=0.0068). We constructed a combined score of molecular data (OPI) and clinical parameters (residual tumour), which was able to define patient groups with highly significant differences in survival. The integrated analysis of gene expression data as well as residual tumour can be used for optimised assessment of prognosis. As traditional treatment options are limited, this analysis may be able to optimise clinical management and to identify those patients that would be candidates for new therapeutic strategies.
Publication Title
A prognostic gene expression index in ovarian cancer - validation across different independent data sets.
Sample Metadata Fields
Specimen part, Disease stage
View Samples- Homo sapiens
- 38 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
STAT1 is overexpressed in tumors selected for radioresistance and confers protection from radiation in transduced sensitive cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Nu61, a radiation-resistant human tumor xenograft, was selected from a parental radiosensitive tumor SCC-61 by eight serial cycles of passage in athymic nude mice and in vivo irradiation.
Publication Title
STAT1 is overexpressed in tumors selected for radioresistance and confers protection from radiation in transduced sensitive cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Nu61, a radiation-resistant human tumor xenograft, was selected from a parental radiosensitive tumor SCC-61 by eight serial cycles of passage in athymic nude mice and in vivo irradiation.
Publication Title
STAT1 is overexpressed in tumors selected for radioresistance and confers protection from radiation in transduced sensitive cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Nu61, a radiation-resistant human tumor xenograft, was selected from a parental radiosensitive tumor SCC-61 by eight serial cycles of passage in athymic nude mice and in vivo irradiation.
Publication Title
STAT1 is overexpressed in tumors selected for radioresistance and confers protection from radiation in transduced sensitive cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
The murine model of Lyme disease provides a unique opportunity to study the localized host response to similar stimulus, B. burgdorferi, in the joints of mice destined to develop severe arthritis (C3H) or mild disease (C57BL/6). Pathways associated with the response to infection and the development of Lyme arthritis were identified by global gene expression patterns using oligonucleotide microarrays. A robust induction of IFN responsive genes was observed in severely arthritic C3H mice at one week of infection, which was absent from mildly arthritic C57BL/6 mice. In contrast, infected C57BL/6 mice displayed a novel expression profile characterized by genes involved in epidermal differentiation and wound repair, which were decreased in the joints of C3H mice. These expression patterns were associated with disease state rather than inherent differences between C3H and C57BL/6 mice, as C57BL/6-IL10-/- mice infected with B. burgdorferi develop more severe arthritis that C57BL/6 mice and displayed an early gene expression profile similar to C3H mice. Gene expression profiles at two and four weeks post infection revealed a common response of all strains that was likely to be important for the host defense to B. burgdorferi and mediated by NF-kB-dependent signaling. The gene expression profiles identified in this study add to the current understanding of the host response to B. burgdorferi and identify two novel pathways that may be involved in regulating the severity of Lyme arthritis.
Publication Title
Gene expression profiling reveals unique pathways associated with differential severity of lyme arthritis.
Sample Metadata Fields
No sample metadata fields
View Samples