In cervical cancer, an important mechanism by which tumour cells escape immune surveillance is loss of HLA class I, enabling tumours to evade recognition and lysis by cytotoxic T lymphocytes. Some tumours, however, escape from immune surveillance without accumulating defects in antigen presentation. We hypothesized that tumours with no or partial loss of HLA class I develop alternative mechanisms to prevent immune surveillance. To investigate this hypothesis, genome-wide expression profiling using Illumina arrays was performed on cervical squamous cell carcinomas showing overall loss of HLA class I, partial and normal HLA class I protein expression. Statistical analyses revealed no significant differences in gene expression between tumours with partial (n = 11) and normal HLA class I expression (n = 10). Comparison of tumours with normal/partial HLA class I expression (n = 21) with those with overall loss of HLA class I expression (n = 11) identified 150 differentially expressed genes. Most of these genes were involved in the defense response (n = 27), and, in particular, inflammatory and acute phase responses. Especially SerpinA1 and SerpinA3 were found to be upregulated in HLA positive tumours (3.6 and 8.2 fold, respectively), and this was confirmed by real-time PCR and immunohistochemistry. In a group of 117 tumours, high SerpinA1 and SerpinA3 expression in association with normal/partial HLA expression correlated significantly with poor overall survival (p = 0.035 and p = 0.05, respectively). This study shows that HLA positive tumours are characterized by a higher expression of genes associated with an inflammatory profile and that expression of the acute phase proteins SerpinA1 and SerpinA3 in HLA positive tumours is associated with worse prognosis.
Elevated expression of SerpinA1 and SerpinA3 in HLA-positive cervical carcinoma.
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Molecular pathway profiling of T lymphocyte signal transduction pathways; Th1 and Th2 genomic fingerprints are defined by TCR and CD28-mediated signaling.
Cell line, Treatment, Time
View SamplesT lymphocytes are orchestrators of adaptive immunity. Nave T cells may differentiate into the Th1, Th2, Th17 or iTreg phenotype, depending on environmental co-stimulatory signals. In order to identify the genes and pathways involved in differentiation of Jurkat T cells towards Th1 and Th2 subtypes we performed comprehensive transcriptome analyses of Jurkat T cells stimulated with various stimuli an pathway inhibitors
Molecular pathway profiling of T lymphocyte signal transduction pathways; Th1 and Th2 genomic fingerprints are defined by TCR and CD28-mediated signaling.
Cell line, Treatment
View SamplesT lymphocytes are orchestrators of adaptive immunity. Nave T cells may differentiate into the Th1, Th2, Th17 or iTreg phenotype, depending on environmental co-stimulatory signals. In order to identify the genes and pathways involved in differentiation of Jurkat T cells towards Th1 and Th2 subtypes we performed comprehensive transcriptome analyses of Jurkat T cells stimulated with various stimuli an pathway inhibitors
Molecular pathway profiling of T lymphocyte signal transduction pathways; Th1 and Th2 genomic fingerprints are defined by TCR and CD28-mediated signaling.
Cell line, Treatment, Time
View SamplesIn mammals body temperature fluctuates diurnally around a mean value of 36-37°C. Despite the small differences between minimal and maximal values, body temperature rhythms can drive robust cycles in gene expression in cultured cells and, likely, in, animals. Here we studied the mechanisms responsible for the temperature-dependent expression of Cold- Inducible RNA-Binding Protein (CIRBP). In NIH3T3 fibroblasts exposed to simulated mouse body temperature cycles Cirbp mRNA oscillates about 3-fold in abundance, as it does in mouse liver. This daily mRNA accumulation cycle is directly controlled by temperature oscillations and does not depend on the cells’ circadian clocks. Here, we show that the temperature-dependent accumulation of Cirbp mRNA is controlled primarily by the regulation of splicing efficiency, defined as the fraction of Cirbp pre-mRNA processed into mature mRNA. As revealed by genome-wide “approach-to-steady-kinetics”, this posttranscriptional mechanism is wide-spread in the temperature-dependent control of gene expression. Overall design: Cultured NIH3T3 cells seeded and kept at 37C degree for 4 hours before being switched to 33C and 38C. After 16 hours of incubation the temperature was shifted to 38C and 33C, respectively. Sample were then taken at 0, 1, 3, 6 and 9 hour after the temperature shift. Paired-end, strand-specific, total RNA-seq was performed over the samples at the respective time points using the Illumina HiSeq2500 platform.
Temperature regulates splicing efficiency of the cold-inducible RNA-binding protein gene Cirbp.
Specimen part, Subject, Time
View SamplesAnalysis of the gene expression profile of the atx1 mutant of Arabidopsis thaliana compared to the wild-type, using apices tissue of in in vitro plants and Affymetrix ATH1 chips.
ARABIDOPSIS TRITHORAX1 dynamically regulates FLOWERING LOCUS C activation via histone 3 lysine 4 trimethylation.
Age, Specimen part
View SamplesThe rod photoreceptor-specific neural retina leucine zipper protein Nrl is essential for rod differentiation and plays a critical role in regulating gene expression. In the mouse retina, rods account for 97% of the photoreceptors; however, in the absence of Nrl (Nrl-/-), no rods are present and a concomitant increase in cones is observed.
Expression profiling of the developing and mature Nrl-/- mouse retina: identification of retinal disease candidates and transcriptional regulatory targets of Nrl.
Specimen part
View SamplesMolecular profiling of 159 lung cancers of different histological subtypes. A primary objective is to identify gene expression differences between histological subtypes. Sample overlap exist with GSE60644
Gene Expression Profiling of Large Cell Lung Cancer Links Transcriptional Phenotypes to the New Histological WHO 2015 Classification.
Sex, Age
View SamplesThe gene expression profile of blood drawn from healthy individuals was studied over a period of six months, at five time points. The gene expression profiles appeared to be constant over one month and to slightly vary over three months. A small proportion of genes were found to be differentially regulated according to gender. Differential gene regulation by age (in subjects 2555 years of age versus subjects > 55 years of age) was not observed.
A longitudinal study of gene expression in healthy individuals.
Sex, Age, Specimen part, Subject
View SamplesT-cell acute lymphoblastic leukemia (T-ALL) is a malignancy of T cell progenitors that in most patients is associated with activating mutations in the NOTCH1 pathway. Recent reports have indicated a link between Ca2+ homeostasis in the endoplasmic reticulum (ER), the regulation of NOTCH1 signaling and T-ALL. Here we investigated the role of store-operated Ca2+ entry (SOCE) in T-ALL. SOCE is a Ca2+ influx pathway that is mediated by the plasma membrane Ca2+ channel ORAI1 and its activators STIM1 and STIM2. Deletion of STIM1 and STIM2 in leukemic cells abolished SOCE and significantly prolonged the survival of mice in a NOTCH1-driven model of T-ALL. The survival advantage was unrelated to leukemia development and leukemic cell burden, but was associated with the SOCE-dependent ability of malignant T lymphoblasts to cause inflammation in leukemia-infiltrated organs. Mice with wildtype T-ALL showed a severe necroinflammatory response in their bone marrow, which was absent in mice with Stim1/2-/- leukemia. Several signaling pathways previously linked to cancer-induced inflammation were downregulated in Stim1/2-/- leukemic cells, likely accounting for less aggressive leukemia progression and prolonged survival of mice. Our study shows that T-ALL is associated with inflammation of leukemia-infiltrated organs and that SOCE controls the proinflammatory effects of leukemic T lymphoblasts. Overall design: Bone marrow leukemic cell were isolated from WT and Stim1/2-/- leukemic mice, 21 days after leukemia induction and their mRNA profiles were generated by deep sequencing, in triplicate.
STIM1 and STIM2 Mediate Cancer-Induced Inflammation in T Cell Acute Lymphoblastic Leukemia.
Specimen part, Cell line, Subject
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