Background: Recently a 76-gene prognostic signature able to predict distant metastases in lymph node-negative (N-) breast cancer patients was reported. The aims of this study conducted by TRANSBIG were to independently validate these results and to compare the outcome with clinical risk assessment. Materials and Methods: Gene expression profiling of frozen samples from 198 N- systemically untreated patients was performed at the Bordet Institute, blinded to clinical data and independent of Veridex. Genomic risk was defined by Veridex, blinded to clinical data. Survival analyses, done by an independent statistician, were performed with the genomic risk and adjusted for the clinical risk, defined by Adjuvant!Online. Results: The actual 5- and 10-year time to distant metastasis (TDM) were 98% (88%-100%) and 94% (83%-98%) respectively for the good profile group and 76% (68%- 82%) and 73% (65%-79%) for the poor profile group. The actual 5- and 10-year overall survival (OS) were 98% (88%-100%) and 87% (73%-94%) respectively for the good profile group and 84% (77%-89%) and 72% (63%-78%) for the poor profile group. We observed a strong time-dependency of this signature, leading to an adjusted HR of 13.58 (1.85-99.63) and 8.20 (1.10-60.90) at 5 years, and 5.11 (1.57-16.67) and 2.55 (1.07-6.10) at 10 years for TDM and OS respectively. Conclusion: This independent validation confirmed the performance of the 76-gene signature and adds to the growing evidence that gene expression signatures are of clinical relevance, especially for identifying patients at high risk of early distant metastases.
Strong time dependence of the 76-gene prognostic signature for node-negative breast cancer patients in the TRANSBIG multicenter independent validation series.
Age, Disease stage
View SamplesWe report two clusters in the overall profiles of expression among the samples. At the parasitemia onset, there is a strong interferon response reflected in up-regulation of co-regulated transcripts, while unexpectedly we also see down-regulation of transcripts related to TLR signaling and innate immunity. RNASeq also suggested differential expression of reticulocytes and a subset of T cell function. No obvious difference in the transcriptomes of naïve and semi-immune volunteers was seen, however several hundred genes were up-regulated in naïve individuals. Overall design: RNA-seq analysis was performed for 12 individuals (6 each from Buenaventura and Cali) for two of the time points, namely the diagnosis day and baseline (pre-challenge day).
Integrative metabolomics and transcriptomics signatures of clinical tolerance to Plasmodium vivax reveal activation of innate cell immunity and T cell signaling.
No sample metadata fields
View SamplesOne of our new major finding among the genes that contributes to MS susceptibility is ICSBP1. The so called disease modifying therapies like interferon-beta (IFN-), possibly acting on the peripheral T-cells, reduce the disease activity and the clinical progression, with a MRI-detectable effect in preventing lesion burden and cerebral atrophy development in RR-MS. It suggests a critical role of peripheral blood mononuclear cells (PBMCs) immune response and modulation in developing inflammation in the brain. We tested the hypothesis that the genetic effect of the susceptible allele ICSBP1 can impact the gene expression profile of molecules belonging to the interferon pathway. We therefore interrogated the PBMC for changes in gene expression profile. We correlate those changes with the minor allele frequency for ICSBP1, performing independent quantitative trait analysis for each treatment category. Expression Quantitative Trait Loci Association with a p value < 0.05 have been used in follow up analysis. The regression coefficient of the Quantitative trait association represents the degree of correlation between the gene expression for each interrogated target gene and the minor allele frequency of the SNP for our gene of interest. This coefficient has been used as input in the subsequent Gene Set Enrichment Analysis performed in a pre-ranked approach. The resulting GSEA-SNP method rests on the assumption that SNPs underlying a disease phenotype might affect genes constituting a signaling pathway or genes with a common regulation. Therefore, GSEA-SNP can facilitate the identification of pathways or of underlying biological mechanisms.
Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci.
Specimen part
View SamplesLRAT knockout mice on vitamin A sufficient or deficient diets were compared to age-matched wildtype mice on a vitamin A sufficient diet
Effects of vitamin A deficiency in the postnatal mouse heart: role of hepatic retinoid stores.
Sex, Specimen part
View SamplesLRAT knockout mice on vitamin A sufficient or deficient diets were compared to age and gender matched wildtype mice on a vitamin A sufficient diet
Effects of vitamin A deficiency in the postnatal mouse heart: role of hepatic retinoid stores.
Sex, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Effects of vitamin A deficiency in the postnatal mouse heart: role of hepatic retinoid stores.
Sex, Specimen part
View SamplesThis data set was generated by the UK Brain Expression Consortium and consists of gene expression data generated from post-mortem human brain samples, dissected from 10 brain regions and originating from a large cohort of neurologically and neuropathologically normal individuals.
Analysis of gene expression data using a linear mixed model/finite mixture model approach: application to regional differences in the human brain.
Sex, Disease, Subject
View SamplesThis data set was generated by the UK Brain Expression Consortium and consists of gene expression data generated from post-mortem human brain samples, dissected from 10 brain regions and originating from a large cohort of neurologically and neuropathologically normal individuals.
Widespread sex differences in gene expression and splicing in the adult human brain.
Sex, Disease, Subject
View SamplesThis data set was generated by the UK Brain Expression Consortium and consists of gene expression data generated from post-mortem human brain samples, dissected from 10 brain regions and originating from a large cohort of neurologically and neuropathologically normal individuals.
Widespread sex differences in gene expression and splicing in the adult human brain.
Sex, Disease, Subject
View SamplesTranscription profiling of wild type, relA-, and relA-spoT-, crp-, dksA-, rpoS-, lrp- mutant strains of E. coli starved for isoleucine
The global, ppGpp-mediated stringent response to amino acid starvation in Escherichia coli.
No sample metadata fields
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