Samples were taken from surgically resected tumor specimens/metastases from patients with colorectal cancer. The expression profiles were determined using the Affymetrix GeneChip Human Exon 1.0 ST Array version 2.
Colorectal Cancer Cell Line Proteomes Are Representative of Primary Tumors and Predict Drug Sensitivity.
Specimen part, Disease, Disease stage, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
High-grade serous ovarian cancer arises from fallopian tube in a mouse model.
Specimen part, Disease, Disease stage
View SamplesThe cell of origin of serious ovarian cancer is unknown. To create a mouse model for this lethal cancer and identify early cancer biomarkers, we conditionally deleted both Dicer (essential for microRNA biosynthesis) and Pten (a negative regulator of the PI3K pathway) in the female reproductive tract. Beginning at ~3-5 months, these Dicer/Pten mutant mice develop high-grade serious carcinomas that initiate in the stroma of the fallopian tube through a mesenchymal-to-epithelial transition (MET), subsequently envelop the ovary, and then metastasize throughout the peritoneum, resulting in ascites and 100% lethality by 13 months. The fallopian tube cancers demonstrate upregulation of genes encoding known and novel secreted proteins that are potential biomarkers. This study uncovers a new paradigm for the initiation of high-grade serous ovarian cancer.
High-grade serous ovarian cancer arises from fallopian tube in a mouse model.
Specimen part, Disease, Disease stage
View SamplesThe cell of origin of serious ovarian cancer is unknown. To create a mouse model for this lethal cancer and identify early cancer biomarkers, we conditionally deleted both Dicer (essential for microRNA biosynthesis) and Pten (a negative regulator of the PI3K pathway) in the female reproductive tract. Beginning at ~3-5 months, these Dicer/Pten mutant mice develop high-grade serious carcinomas that initiate in the stroma of the fallopian tube through a mesenchymal-to-epithelial transition (MET), subsequently envelop the ovary, and then metastasize throughout the peritoneum, resulting in ascites and 100% lethality by 13 months. The fallopian tube cancers demonstrate upregulation of genes encoding known and novel secreted proteins that are potential biomarkers. This study uncovers a new paradigm for the initiation of high-grade serous ovarian cancer.
High-grade serous ovarian cancer arises from fallopian tube in a mouse model.
Specimen part, Disease, Disease stage
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Systems genetics identifies a co-regulated module of liver microRNAs associated with plasma LDL cholesterol in murine diet-induced dyslipidemia.
No sample metadata fields
View SamplesGenetic variation, in addition to environmental influences like diet, can govern the expression levels of microRNAs (miRNAs). MiRNAs are commonly found to operate cooperatively in groups to regulate gene expression. To investigate this, we combined small RNA sequencing, clinical phenotypes, and microarray data measuring gene expression from an outbred mouse model, the Diversity Outbred population. In the DO population, each individual has a distinct genome that is a mosaic of 8 inbred founder strains. We used these data to identify co-regulated modules of miRNAs and genes that are influenced by genetics and diet, and identify relationships between the modules and phenotypes in over 200 DO mice.
Systems genetics identifies a co-regulated module of liver microRNAs associated with plasma LDL cholesterol in murine diet-induced dyslipidemia.
No sample metadata fields
View SamplesHigh-throughput genomic studies have identified thousands of genetic alterations in colorectal cancer (CRC). Distinguishing driver from passenger mutations is critical for developing rational therapeutic strategies. Because only a few transcriptional subtypes exist in previously studied tumor types, we hypothesize that highly heterogeneous genomic alterations may converge to a limited number of distinct mechanisms that drive unique gene expression patterns in different transcriptional subtypes. In this study, we defined transcriptional subtypes for CRC and identified driver networks/pathways for each subtype, respectively. Applying consensus clustering to a patient cohort with 1173 samples identified three transcriptional subtypes, which were validated in an independent cohort with 485 samples. The three subtypes were characterized by different transcriptional programs related to normal adult colon, early colon embryonic development, and epithelial mesenchymal transition, respectively. They also showed statistically different clinical outcomes. For each subtype, we mapped somatic mutation and copy number variation data onto an integrated signaling network and identified subtype-specific driver networks using a random walk-based strategy. We found that genomic alterations in the Wnt signaling pathway were common among all three subtypes; however, unique combinations of pathway alterations including Wnt, VEGF, Notch and TGF-beta drove distinct molecular and clinical phenotypes in different CRC subtypes. Our results provide a coherent and integrated picture of human CRC that links genomic alterations to molecular and clinical consequences, and which provides insights for the development of personalized therapeutic strategies for different CRC subtypes.
Deciphering genomic alterations in colorectal cancer through transcriptional subtype-based network analysis.
No sample metadata fields
View SamplesWe analyzed gene expression in human fibroblasts stimulated by platelet-derived growth factor-BB (PDGF-BB) or basic fibroblast growth factor (bFGF) for 1h and 24h. The results of two independent experiments were merged. SAM analysis identified 116 relevant probe sets. Hierarchical clustering of these probe sets showed divergent early gene regulation by PDGF and FGF but overlapping late response. We first analyzed genes commonly regulated by PDGF-BB and b-FGF more than 2 fold after 24h of stimulation and we found that these two growth factors repressed FOXO.
The transcription of FOXO genes is stimulated by FOXO3 and repressed by growth factors.
No sample metadata fields
View SamplesRecent studies have shown that circular RNAs (circRNAs) are abundant, widely expressed in mammals, and can display cell-type specific expression. However, how production of circRNAs is regulated and their precise biological function remains largely unknown. To study how circRNAs might be regulated during colorectal cancer progression, we used three isogenic colon cancer cell lines that differ only in KRAS mutation status. Cellular RNAs from the parental DLD-1 cells that contain both wild-type and G13D mutant KRAS alleles and isogenically-matched derivative cell lines, DKO-1 (mutant KRAS allele only) and DKs-8 (wild-type KRAS allele only) were analyzed using RNA-Seq. We developed a bioinformatics pipeline to identify and evaluate circRNA candidates from RNA-Seq data. Hundreds of high-quality circRNA candidates were identified in each cell line. Remarkably, circRNAs were significantly down-regulated at a global level in DLD-1 and DKO-1 cells compared to DKs-8 cells, indicating a widespread effect of mutant KRAS on circRNA abundance. This finding was confirmed in two independent colon cancer cell lines HCT116 (KRAS mutant) and HKe3 (KRAS WT). In all three cell lines, circRNAs were also found in secreted extracellular-vesicles, and circRNAs were more abundant in exosomes than cells. Our results suggest that circRNAs may serve as promising cancer biomarkers. Overall design: RNAseq deep sequencing for both cell and exosome mRNAs
Circular RNAs are down-regulated in KRAS mutant colon cancer cells and can be transferred to exosomes.
No sample metadata fields
View SamplesThe aim of this study was to identify genes regulated by IL-12, IL-18 and IFN-alpha during early differentiation of human Th1 cells
Activating transcription factor 3 is a positive regulator of human IFNG gene expression.
Specimen part
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