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GSE50081
Homo sapiens
178 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background: Patients with early stage non-small cell lung carcinoma (NSCLC) may benefit from treatments based on more accurate prognosis. A 15-gene prognostic classifier for NSCLC was identified from mRNA expression profiling of tumor samples from the NCIC CTG JBR.10 trial. Here, we assessed its value in an independent set of cases.
Publication Title
Validation of a histology-independent prognostic gene signature for early-stage, non-small-cell lung cancer including stage IA patients.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 28 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Purpose: To explore intratumor heterogeneity in gene expression profiles from patients with cervical cancer.
Publication Title
Gene expression profiling in cervical cancer: an exploration of intratumor heterogeneity.
Sample Metadata Fields
Age, Disease stage
View Samples- Homo sapiens
- 133 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Purpose: The JBR.10 trial demonstrated benefit from adjuvant cisplatin/vinorelbine (ACT) in early-stage non-small-cell lung cancer (NSCLC). We hypothesized that expression profiling may identify stage-independent subgroups who might benefit from ACT.
Publication Title
Prognostic and predictive gene signature for adjuvant chemotherapy in resected non-small-cell lung cancer.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 59 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
The tumor microenvironment strongly influences cancer development, progression and metastasis. The role of carcinoma-associated fibroblasts (CAFs) in these processes and their clinical impact has not been studied systematically in non-small cell lung carcinoma (NSCLC). We established primary cultures of CAFs and matched normal fibroblasts (NFs) from 15 resected NSCLC. We demonstrate that CAFs have greater ability than NFs to enhance the tumorigenicity of lung cancer cell lines. Microarray gene expression analysis of the 15 matched CAF and NF cell lines identified 46 differentially expressed genes, encoding for proteins that are significantly enriched for extracellular proteins regulated by the TGF-beta signaling pathway. We have identified a subset of 11 genes that formed a prognostic gene expression signature, which was validated in multiple independent NSCLC microarray datasets. Functional annotation using protein-protein interaction analyses of these and published cancer stroma-associated gene expression changes revealed prominent involvement of the focal adhesion and MAPK signalling pathways. Fourteen (30%) of the 46 genes also were differentially expressed in laser-capture micro-dissected corresponding primary tumor stroma compared to the matched normal lung. Six of these 14 genes could be induced by TGF-beta1 in NF. The results establish the prognostic impact of CAF-associated gene expression changes in NSCLC patients.
Publication Title
Prognostic gene-expression signature of carcinoma-associated fibroblasts in non-small cell lung cancer.
Sample Metadata Fields
Sex, Age, Disease, Disease stage, Cell line
View Samples- Homo sapiens
- 29 Downloadable Samples
Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
The tumor microenvironment strongly influences cancer development, progression and metastasis. The role of carcinoma-associated fibroblasts (CAFs) in these processes and their clinical impact has not been studied systematically in non-small cell lung carcinoma (NSCLC). We established primary cultures of CAFs and matched normal fibroblasts (NFs) from 15 resected NSCLC. We demonstrate that CAFs have greater ability than NFs to enhance the tumorigenicity of lung cancer cell lines. Microarray gene expression analysis of the 15 matched CAF and NF cell lines identified 46 differentially expressed genes, encoding for proteins that are significantly enriched for extracellular proteins regulated by the TGF-beta signaling pathway. We have identified a subset of 11 genes that formed a prognostic gene expression signature, which was validated in multiple independent NSCLC microarray datasets. Functional annotation using protein-protein interaction analyses of these and published cancer stroma-associated gene expression changes revealed prominent involvement of the focal adhesion and MAPK signalling pathways. Fourteen (30%) of the 46 genes also were differentially expressed in laser-capture micro-dissected corresponding primary tumor stroma compared to the matched normal lung. Six of these 14 genes could be induced by TGF-beta1 in NF. The results establish the prognostic impact of CAF-associated gene expression changes in NSCLC patients.
Publication Title
Prognostic gene-expression signature of carcinoma-associated fibroblasts in non-small cell lung cancer.
Sample Metadata Fields
Sex, Age, Disease, Disease stage, Cell line
View Samples- Homo sapiens
- 30 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
The tumor microenvironment strongly influences cancer development, progression and metastasis. The role of carcinoma-associated fibroblasts (CAFs) in these processes and their clinical impact has not been studied systematically in non-small cell lung carcinoma (NSCLC). We established primary cultures of CAFs and matched normal fibroblasts (NFs) from 15 resected NSCLC. We demonstrate that CAFs have greater ability than NFs to enhance the tumorigenicity of lung cancer cell lines. Microarray gene expression analysis of the 15 matched CAF and NF cell lines identified 46 differentially expressed genes, encoding for proteins that are significantly enriched for extracellular proteins regulated by the TGF-beta signaling pathway. We have identified a subset of 11 genes that formed a prognostic gene expression signature, which was validated in multiple independent NSCLC microarray datasets. Functional annotation using protein-protein interaction analyses of these and published cancer stroma-associated gene expression changes revealed prominent involvement of the focal adhesion and MAPK signalling pathways. Fourteen (30%) of the 46 genes also were differentially expressed in laser-capture micro-dissected corresponding primary tumor stroma compared to the matched normal lung. Six of these 14 genes could be induced by TGF-beta1 in NF. The results establish the prognostic impact of CAF-associated gene expression changes in NSCLC patients.
Publication Title
Prognostic gene-expression signature of carcinoma-associated fibroblasts in non-small cell lung cancer.
Sample Metadata Fields
Sex, Age, Disease, Disease stage
View Samples- Caenorhabditis elegans
- 20 Downloadable Samples
Illumina HiSeq 2500
Description
Purpose: The goal of this study is to understand how dbl-1, which is made primarily in neurons, and hrg-7, which is exclusively made in the intestine, contribute to systemic heme homeostasis. Methods: mRNA profiles of late L4 dbl-1(nk3) and hrg-7(tm6801) mutant C. elegans fed OP50 E. coli or OP50 + 50µM heme were compared to mRNA profiles from wildtype (WT) broodmates. Profiles were generated with single-end 50 base reads obtained using Illumina’s HiSeq 2500. Bioinformatics quality control was performed followed by alignment of reads to the ce10 reference genome using Tophat2, version 2.1.0. We found differentially expressed genes using Cufflinks 2, version 2.2.1 with a cutoff of 0.05 on False Discovery Rate (FDR). Results: We found a substantial overlap of genes regulated by both dbl-1 and hrg-7, including 49 heme-responsive genes (hrgs) in low heme (OP50) and 11 hrgs in high heme (OP50 + 50µM). Additionally, our data indicate crosstalk between dbl-1 and hrg-7 signaling. dbl-1 directly regulates hrg-7 expression, while hrg-7 regulates three components of the dbl-1 signaling pathway. Conclusions: Our study demonstrates that communication between the neuron and intestine is essential for heme homeostasis. Specifically, we report that HRG-7 functions as a secreted signaling factor which communicates intestinal heme status with extraintestinal tissues by integrating a DBL-1/BMP -dependent response from the neurons to transcriptionally regulate genes involved in heme homeostasis. Cellular requirements for heme are fulfilled by a cell’s internal capacity to synthesize its own heme in a cell-autonomous manner. However, growing evidence in vertebrates predicts that cellular heme levels in animals are not only maintained by heme synthesis, but also by distally located proteins that could signal systemic heme requirements to an inter-organ heme trafficking network through cell-nonautonomous regulation. Using C. elegans, a genetically and optically amenable animal model for visualizing heme-dependent signaling, we show that HRG-7, an aspartic protease homolog, mediates inter-organ signaling between the intestine and neuron. Loss of hrg-7 results in robust expression of intestinal heme importers and, remarkably, this occurs even under heme replete conditions when such transporters are not normally expressed. HRG-7 functions as a secreted signaling factor, independent of a functional enzymatic active site, and communicates intestinal heme status with extraintestinal tissues by integrating a DBL-1/BMP -dependent response from the neurons to transcriptionally regulate intestinal heme homeostasis. Given the evidence indicating that mechanisms of heme transport are conserved across metazoa, it is conceivable that the cell-nonautonomous signaling framework that we uncovered in C. elegans may have functional relevance for inter-organ regulation of iron and heme metabolism in humans. Overall design: Comparison of mRNA profiles from dbl-1(nk3) mutant C. elegans vs. wildtype (WT) broodmates and hrg-7(tm6801) mutants vs (WT) broomates fed OP50 E. coli or OP50 + 50µM heme. Biological duplicates were analyzed for dbl-1(nk3) mutants and (WT) broodmates. Biological triplicates were analyzed for hrg-7(tm6801) mutants and (WT) broodmates.
Publication Title
Inter-organ signalling by HRG-7 promotes systemic haem homeostasis.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 92 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
We evaluated transcriptional profiles in peripheral blood mononuclear cells (PBMCs) from 54 pregnant women in Kenya, 19 of whom delivered preterm.
Publication Title
Influenza-Induced Interferon Lambda Response Is Associated With Longer Time to Delivery Among Pregnant Kenyan Women.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 2 Downloadable Samples
Description
CTCF is a master regulator that plays a role in genome architecture and gene expression. A key aspect of CTCF’s mechanism involves bringing together distant genetic elements for intra- and inter-chromosomal interactions. Evidence from epigenetic processes, such as X-chromosome inactivation (XCI), suggests that CTCF may carry out its functions through interacting RNAs. Using genome-wide approaches to investigate the relationship between CTCF’s RNA interactome and its epigenomic landscape, here we report that CTCF interacts with thousands of transcripts in mouse embryonic stem cells (mESC), many in close proximity to CTCF’s genomic binding sites. Biochemical analysis demonstrates that CTCF is a high-affinity RNA binding protein that contacts RNA directly and specifically. In the XCI model, CTCF binds the active and inactive X-chromosomes allele-specifically. At the X-inactivation center, Tsix RNA binds CTCF and targets CTCF to a region associated with X-chromosome pairing. Our work implicates CTCF-RNA interactions in long-range chromosomal interactions in trans and adds a new layer of complexity to CTCF regulation. The genome-wide datasets reported here will provide a useful resource for further study of CTCF-mediated epigenomic regulation. Overall design: CTCF RNA interactome was identified by UV-crosslinking and immunoprecipitation followed by high-throughput sequencing (CLIP-seq), and was compared to CTCF''s epigenomic landscape as obtained by chromatin immunoprecipitation (ChIP-seq).
Publication Title
Locus-specific targeting to the X chromosome revealed by the RNA interactome of CTCF.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
E-cadherin, a protein encoded by the CDH1 gene is the dominant epithelial cell adhesion molecule playing a crucial role in epithelial tissue polarity and structural integrity. The progression of 90% or more carcinomas is believed to be mediated by disruption of normal E-cadherin expression, subcellular localization or function. Despite the strong correlation between E-cadherin loss and malignancy the mechanism through how this occurs is not known in most sporadic and hereditary epithelial carcinomas. Previous works have shown the importance of CDH1 intron 2 sequences for proper gene and protein expression supporting the possibility of these being cis-modulators of E-cadherin expression/function. but when co-expressed it led to reduced cell-cell adhesiveness, increased invasion and angiogenesis. By expression array analysis, IFITM1 and IFI27 levels were found to be increased upon CDH1a overexpression. Importantly, CDH1a was found to be de novo expressed in gastric cancer cell lines when compared to normal stomach.
Publication Title
Transcription initiation arising from E-cadherin/CDH1 intron2: a novel protein isoform that increases gastric cancer cell invasion and angiogenesis.
Sample Metadata Fields
Specimen part, Cell line
View Samples