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.
A prognostic gene expression index in ovarian cancer - validation across different independent data sets.
Specimen part, Disease stage
View SamplesIn this work we have analyzed the transcriptomic profiles of E9 mouse embryos. We show that Hoxd1 and Haglr transcripts are absent after targeted deletion of the CpG: 114 island. Overall design: RNA-seq analysis of trunk from the anterior limit of the forelimb bud to the tailbud, aiming to exclude all extra-embryonic, head, cervical and heart tissues. Individuals 443 (wt) and 445 (Del(CpG114) homozygous), were siblings from the same dam, while biological replicates 456 (wt) and 455 (Del(CpG114) homozygous) were siblings from another dam.
Control of growth and gut maturation by <i>HoxD</i> genes and the associated lncRNA <i>Haglr</i>.
Specimen part, Cell line, Subject
View SamplesHox genes are required during the morphogenesis of both vertebrate digits and external genitals.We investigated whether transcription in such distinct contexts involves a shared enhancer-containing landscape. We show that the same regulatory topology is used, yet with some tissue-specific enhancer-promoter interactions, suggesting the hijacking of a regulatory backbone from one context to the other. In addition, comparable organizations are observed at both HoxA and HoxD clusters, which separated through genome duplication in an ancestral invertebrate animal.We propose that this convergent regulatory evolution was triggered by the pre-existence of some chromatin architecture, thus facilitating the subsequent recruitment of the appropriate transcription factors. Such regulatory topologies may have both favored and constrained the evolution of pleiotropic developmental loci in vertebrates. Overall design: RNA-seq from mouse E12.5 digits cells and mouse E15.5 genital tubercle cells.
Convergent evolution of complex regulatory landscapes and pleiotropy at Hox loci.
No sample metadata fields
View SamplesWe report cell type specific Nova HITS-CLIP using BAC-transgenic lines expressing GFP-Nova under the motor neuron specific choline acetyltransferase (Chat) promoter. By comparing transcriptome wide Nova binding map in motor neurons and that in the whole spinal cord, we identified differential Nova binding sites in motor neurons, which correlate with motor neuron specific RNA processing. Overall design: 14 total samples were analyzed. For HITS-CLIP, 4 biological replicates were performed for each BAC-transgenic line, as well as the whole spinal cord. For RNA-seq, 2 biological repliates were performed on the whole spinal cord.
Cell type-specific CLIP reveals that NOVA regulates cytoskeleton interactions in motoneurons.
No sample metadata fields
View SamplesMyelinating glia in the auditory system enclose auditory nerve fibers, providing an insulating effect that facilitates rapid transfer of auditory information from the ear to the brain. Here we show that noise exposure at the levels sufficient for inducing hearing loss cause a rapid cellular and molecular response on myelinating glia that precedes neuron degeneration. The response is characterized by inflammatory response, myelin dysmorphology and widespread changes in myelin-related gene expression. Another characteristic was change in expression of the quaking gene (QKI), which encodes a group of RNA binding proteins that are enriched in myelinating glia. Changes in QKI were accompanied by changes in numerous known and potential QKI target genes, including many genes associated with myelination. Our results implicate QKI as a critical early component in the noise response, influencing glia dysfunction that leads to auditory nerve demyelination and, ultimately, sensorineural hearing loss.
Noise-induced dysregulation of <i>Quaking</i> RNA binding proteins contributes to auditory nerve demyelination and hearing loss.
Sex, Specimen part, Time
View SamplesEffects of the prop-1 and Ghrhr mutations in gene expression during normal aging in mice.
Gene expression profile of long-lived Ames dwarf mice and Little mice.
Sex, Age, Specimen part, Disease, Disease stage
View SamplesGender-specific alterations in gene expression and loss of liver sexual dimorphism in the long-lived Ames dwarf mice.
Gender-specific alterations in gene expression and loss of liver sexual dimorphism in the long-lived Ames dwarf mice.
Sex, Age, Specimen part
View SamplesWe report that cellular ROS enzymatically generated in response to contact with lactobacilli in both mice and Drosophila has salutary effects against exogenous insults to the intestinal epithelium via the activation of Nrf2 responsive cytoprotective genes. Overall design: RNA was isolated from the colons of untreated, PBS, E. coli, and LGG innoculated germ free mice and RNA-seq performed to identify the gene expression in response to each condition
Lactobacillus rhamnosus GG-induced Expression of Leptin in the Intestine Orchestrates Epithelial Cell Proliferation.
Age, Specimen part, Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Elevated interferon gamma signaling contributes to impaired regeneration in the aged liver.
Sex, Treatment
View SamplesThe process of liver regeneration can be divided into a series of stages that include initial inductive or priming events through cellular mitosis. Following two-thirds liver resection, the liver undergoes the priming phase, in which cytokines TNF-a and IL-6 activate their respective receptors in hepatocytes. This leads to the activation of several key transcription factors: NF-kB, AP-1, Stat 3, Stat 1, and C/EBP-b and -d . These transcription factors induce the expression of immediate early genes. HGF is also expressed at this time and involved in the transition of quiescent hepatocytes into the G1 phase of the cell cycle. During the G1 phase, delayed early genes are expressed followed by induction of cell cyclerelated genes, both of which require new protein synthesis for their production. Increased expression of FoxM1B and TGF-a occurs at the G1/S transition and is correlated with increased expression of cyclinD1 and decreased expression of cdk inhibitors. During the G2/M phase of the cell cycle, FoxM1B directly elevates cyclinB1, cyclinB2, and cdc25B expression. Additionally, FoxM1B is associated with increased cyclinF and p55cdc, which are involved in completion of the cell cycle following partial hepatectomy. In mice, two-thirds partial hepatectomy promotes proliferation of liver cells and rapid growth of the remaining liver tissue, resulting in complete restoration of organ mass in approximately 7 days (Mackey S. et al. Hepatology 2003 Dec;38(6):1349-52).
Elevated interferon gamma signaling contributes to impaired regeneration in the aged liver.
Sex, Treatment
View Samples