While VEGF-targeted therapies are showing promise in clinical studies, new angiogenesis targets are needed to make additional gains. Here, we show that increased Zeste homologue 2 (EZH2) expression in either tumor cells or in tumor vasculature is predictive of poor clinical outcome. The increase in endothelial EZH2 is a direct result of VEGF stimulation and indicates the presence of a paracrine circuit that promotes angiogenesis by methylating and silencing vasohibin 1 (VASH1). EZH2 silencing in the tumor-associated endothelial cells resulted in inhibition of angiogenesis mediated by reactivation of VASH1, and reduced ovarian cancer growth. Combined, these data provide a new understanding of the regulation of tumor angiogenesis and support the potential for targeting EZH2 as a novel therapeutic approach.
Regulation of tumor angiogenesis by EZH2.
No sample metadata fields
View SamplesGene expression profile of cancer cell lines of breast, lung, pancreatic, gasctric, ovarian, hepatocellular, prostate carcinomas and melanomas.
Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations.
No sample metadata fields
View SamplesPhenotypic and functional changes seen in the aged adaptive immune system are primarily driven by aging of hematopoietic stem cells (HSCs), pharmacological rejuvenated aged HSCs were able to reconstituted a youthful immune system Overall design: We employed RNA-seq to assess similarities/differences between naive CD4+ T cells and CD19+ B cells isolated from RAG1-/- recipients transplanted with either young, old or old rejuvenated (CASIN treated) HSCs
Aged murine hematopoietic stem cells drive aging-associated immune remodeling.
Specimen part, Cell line, Subject
View SamplesThe 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.
Genome-wide gene expression profiling of formalin-fixed paraffin-embedded breast cancer core biopsies using microarrays.
Disease stage
View SamplesGastric 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.
Vascular CXCR4 expression - a novel antiangiogenic target in gastric cancer?
Sex, Age, Specimen part
View SamplesOvarian 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 SamplesThe intestinal immune system must elicit robust immunity against harmful pathogens but restrain immune responses directed against commensal microbes and dietary antigens. The mechanisms that maintain this dichotomy are poorly understood. Here we describe a population of CD11b+F4/80+CD11c macrophages in the lamina propria (LP) that express several anti-inflammatory molecules including interleukin 10 (IL-10), but little or no pro-inflammatory cytokines, even upon stimulation with Toll-like receptor (TLR) ligands. These macrophages induced, in a manner dependent on IL-10, retinoic acid and exogenous transforming growth factor-, differentiation of FoxP3+ regulatory T cells. In contrast, LP CD11b+ dendritic cells elicited IL-17 production. This IL-17 production was suppressed by LP macrophages, indicating that a dynamic interplay between these subsets may influence the balance between immune activation and tolerance.
Lamina propria macrophages and dendritic cells differentially induce regulatory and interleukin 17-producing T cell responses.
No sample metadata fields
View SamplesThe FinHER trial is a multicentre phase 3 randomised adjuvant breast cancer trial that enrolled 1010 patients. The women were randomly assigned to receive three cycles of docetaxel or vinorelbine, followed by three cycles of fluorouracil, epirubicin, and cyclophosphamide.
Integrative proteomic and gene expression analysis identify potential biomarkers for adjuvant trastuzumab resistance: analysis from the Fin-her phase III randomized trial.
Age, Disease stage
View SamplesActivation of inflammatory pathways in human IBD
Activation of an IL-6:STAT3-dependent transcriptome in pediatric-onset inflammatory bowel disease.
No sample metadata fields
View SamplesWomen suffer chronic pain more frequently than men. It is not clear whether this is due to differences in higher level cognitive processes or basic nociceptive responses. This study used a mouse model to dissociate these factors and found no differences in peripheral afferent neurons or in the spinal cord immune response to neuropathic injury. However, it did identify potential sexual dimorphisms in peripheral adaptive immune responses. Overall design: RNA-seq of naïve FACS-purified DRG neurons and MACS-purified DRG neurons after partial sciatic nerve ligation (day 8): comparison of male versus female samples
Sex differences in peripheral not central immune responses to pain-inducing injury.
Sex, Specimen part, Cell line, Subject
View Samples