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GSE21653
Homo sapiens
265 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Medullary breast cancers (MBC) display a basal profile, but a favorable prognosis. We hypothesized that a previously published 368-gene expression signature associated with MBC might serve to define a prognostic classifier in basal cancers. We collected public gene expression and histoclinical data of 2145 invasive early breast adenocarcinomas. We developed a Support Vector Machine (SVM) classifier based on this 368-gene list in a learning set, and tested its predictive performances in an independent validation set. Then, we assessed its prognostic value and that of six prognostic signatures for disease-free survival (DFS) in the remaining 2034 samples. The SVM model accurately classified all MBC samples in the learning and validation sets. A total of 466 cases were basal across other sets. The SVM classifier separated them into two subgroups, subgroup 1 (resembling MBC) and subgroup 2 (not resembling MBC). Subgroup 1 exhibited 71% 5-year DFS, whereas subgroup 2 exhibited 50% (p=9.93E-05). The classifier outperformed the classical prognostic variables in multivariate analysis, conferring lesser risk for relapse in subgroup 1 (HR=0.52, p=3.9E-04). This prognostic value was specific to the basal subtype, in which none of the other prognostic signatures was informative.
Publication Title
A gene expression signature identifies two prognostic subgroups of basal breast cancer.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 197 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Inflammatory breast cancer (IBC) is an aggressive form of BC poorly defined at the molecular level. We compared the molecular portraits of 63 IBC and 134 non-IBC (nIBC) clinical samples. Genomic imbalances of 49 IBCs and 124 nIBCs were determined using high-resolution array-comparative genomic hybridization, and mRNA expression profiles of 197 samples using whole-genome microarrays. Genomic profiles of IBCs were as heterogeneous as those of nIBCs, and globally relatively close. However, IBCs showed more frequent complex patterns and a higher percentage of genes with CNAs per sample. The number of altered regions was similar in both types, although some regions were altered more frequently and/or with higher amplitude in IBCs. Many genes were similarly altered in both types; however, more genes displayed recurrent amplifications in IBCs.
Publication Title
High-resolution comparative genomic hybridization of inflammatory breast cancer and identification of candidate genes.
Sample Metadata Fields
Age
View Samples- Homo sapiens
- 55 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
15-25% of breast cancers (BC) show ERBB2-amplification and overexpression of the encoded ERBB2 tyrosine kinase receptor. They are associated with a poor prognosis but can benefit from targeted therapy. A better knowledge of these BCs may help understand their behavior and design new therapeutic strategies. In this study, we defined the high resolution genome and gene expression profiles of 54 ERBB2-amplified BCs using 244K oligonucleotide array-comparative genomic hybridization and whole-genome DNA microarrays. We first identified the ERBB2-C17orf37-GRB7 genomic segment as the minimal common amplicon, and CRKRS and IKZF3 as the most frequent centromeric and telomeric amplicon borders, respectively. Second, we identified 17 genome regions affected by copy number aberration (CNA). The expression of 37 genes of these regions was deregulated. Third, two types of heterogeneity were observed in ERBB2-amplified BCs. The genomic profiles of estrogen receptor-postive (ER+) and negative (ER-) ERBB2-amplified BCs were different. The WNT/-catenin signaling pathway was involved in ER- ERBB2-amplified BCs, and PVT1 and TRPS1 were candidate oncogenes associated with ER+ ERBB2-amplified BCs. The size of the ERBB2-amplicon was different in inflammatory (IBC) and non inflammatory BCs. ERBB2-amplified IBCs were characterized by the downregulated and upregulated mRNA expression of ten and two genes in proportion to CNA, respectively. We have shown that ERBB2 BCs are heterogeneous and identified genomic features that may be useful in the design of therapeutical strategies
Publication Title
Genome profiling of ERBB2-amplified breast cancers.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 19 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
A major impediment to the effective treatment of patients with PDAC (Pancreatic Ductal Adenocarcinoma) is the molecular heterogeneity of the disease, which is reflected in an equally diverse pattern of clinical responses to therapy. We developed an efficient strategy in which PDAC samples from 17 consecutively patients were obtained by EUS-FNA or surgery, their cells maintained as a primary culture and tumors as breathing tumors by xenografting in immunosuppressed mice. For these patients a clinical follow up was obtained. On the breathing tumors we studied the RNA expression profile by an Affymetrix approach. We observed a significant heterogeneity in their RNA expression profile, however, the transcriptome was able to discriminate patients with long- or short-time survival which correspond to moderately- or poorly-differentiated PDAC tumors respectively. Cells allowed us the possibility to analyze their relative sensitivity to several anticancer drugs in vitro by developing a chimiogram, like an antibiogram for microorganisms, with several anticancer drugs for obtaining an individual profile of drug sensitivity and as expected, the response was patient-dependent. Interestingly, using this approach, we also found that the transcriptome analysis could predict the sensitivity to some anticancer drugs of patients with a PDAC. In conclusion, using this approach, we found that the transcriptome analysis could predict the sensitivity to some anticancer drugs and the clinical outcome of patients with a PDAC.
Publication Title
Transcriptomic analysis predicts survival and sensitivity to anticancer drugs of patients with a pancreatic adenocarcinoma.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 41 Downloadable Samples
Illumina HiSeq 2500
Description
We analyzed the transcriptome of the C57BL/6J mouse hypothalamus, hippocampus, neocortex, and cerebellum to determine estrous cycle-specific changes in these four brain regions. We found almost 16,000 genes are present in one or more of the brain areas but only 210 genes, ~1.3%, are significantly changed as a result of the estrous cycle. The hippocampus has the largest number of differentially expressed genes (DEGs) (82), followed by the neocortex (76), hypothalamus (63), and cerebellum (26). Most of these DEGs (186/210) are differentially expressed in only one of the four brain regions. A key finding is the unique expression pattern of growth hormone (Gh) and prolactin (Prl). Gh and Prl are the only DEGs to be expressed during only one stage of the estrous cycle (metestrus). To gain insight into the function of the DEGs, we examined gene ontology and phenotype enrichment and found significant enrichment for genes associated with myelination, hormone stimulus, and abnormal hormone levels. Additionally, 61 of the 210 DEGs are known to change in response to estrogen in the brain. 50 genes differentially expressed as a result of the estrous cycle are related to myelin and oligodendrocytes and 12 of the 63 DEGs in the hypothalamus are oligodendrocyte- and myelin-specific genes. This transcriptomic analysis reveals that gene expression in the female mouse brain is remarkably stable during the estrous cycle and demonstrates that the genes that do fluctuate are functionally related. Overall design: Hypothalamus, hippocampus, neocortex, and cerebellum mRNA from adult female C57BL/6J (B6) mice were analyzed by RNA sequencing of 3 biological replicates for each of the 4 stages of the estrous cycle using an Illumina HiSeq 2500
Publication Title
The stability of the transcriptome during the estrous cycle in four regions of the mouse brain.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 29 Downloadable Samples
- Illumina HiSeq 2500
Description
A variety of neurological disorders, including Alzheimer's disease, Parkinson's disease, major depressive disorder, dyslexia and autism, are differentially prevalent between females and males. To better understand the possible molecular basis for the sex-biased nature of neurological disorders, we measured both mRNA and protein in the hippocampus of female and male mice at 1, 2, and 4 months of age with RNA-sequencing and mass-spectrometry respectively. Differential expression analyses identify 2699 genes that are differentially expressed between animals of different ages. 198 transcripts are differentially expressed between females and males at one or more ages. The number of transcripts that are differentially expressed between females and males is greater in adult animals than in younger animals. Additionally, we identify 69 transcripts that show complex and sex-specific patterns of temporal regulation across all ages, 8 of which are heat-shock proteins. We also find a modest correlation between levels of mRNA and protein in the mouse hippocampus (Rho = 0.53). This study adds to the substantial body of evidence for transcriptomic regulation in the hippocampus during postnatal development. Additionally, this analysis reveals sex differences in the transcriptome of the developing mouse hippocampus, and further clarifies the need to include both female and male mice in longitudinal studies involving molecular changes in the hippocampus. Overall design: Hippocampal mRNA from 1, 2, and 4 month old male and female B6 mice were analyzed by RNA sequencing of 5 biological replicates using an Illumina HiSeq 2500
Publication Title
Sex differences in the molecular signature of the developing mouse hippocampus.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 26 Downloadable Samples
- Illumina HiSeq 2500
Description
Numerous neurological disorders, including Alzheimer's disease, display a sex-biased prevalence. To identify molecular correlates of this sex bias, we investigated sex-differences in molecular pathology in the hippocampus using the 5XFAD mouse model of Alzheimer's disease during early stages of disease progression (1, 2, and 4 months of age). Overall design: Hippocampal mRNA from 1, 2, and 4 month old male and female 5XFAD mice were analyzed by RNA sequencing of 5 biological replicates using an Illumina HiSeq 2500
Publication Title
Sex-biased hippocampal pathology in the 5XFAD mouse model of Alzheimer's disease: A multi-omic analysis.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 34 Downloadable Samples
- Illumina HiSeq 2500
Description
Identifying sex differences in gene expression within the brain is critical for determining why multiple neurological and behavioral disorders differentially affect males and females. Several are more common or severe in males (e.g., autism and schizophrenia) or females (e.g., Alzheimer’s disease and depression). We analyzed transcriptomic data from the mouse hippocampus of six inbred strains (129S1/SvImJ, A/J, C57BL/6J, DBA/1J, DBA/2J and PWD/Ph), to provide a perspective on differences between male and female gene expression. Our data show that: 1) significant gene expression differences in males versus females varies substantially across the strains, 2) 12 genes exist that are differentially expressed across the inbred strains (termed core genes), and 3) there are >2,600 significantly differentially expressed genes (DEGs) among the strains (termed non-core genes). We found that DBA/2J uniquely has a substantial majority (89%) of DEGs that are more highly expressed in females than males; 129/SvImJ is the most strongly male-biased with a majority (69%) of DEGs that are more highly expressed in males. To gain insight into the sex-biased DEGs, we examined gene ontology, pathway and phenotype enrichment and found significant enrichment in phenotypes related to abnormal nervous system morphology and physiology, among others. In addition, several pathways are enriched significantly, including Alzheimer’s disease (AD), with 32 genes implicated in AD, 8 of which are male-biased. Three of the male-biased genes have been implicated in a neuroprotective role in AD. Our transcriptomic data provide new insight into understanding the possible genetic bases for sex-specific susceptibility and severity of brain disorders. Overall design: Hippocampal mRNA from adult males and females of six inbred strains of mice were analyzed by RNA sequencing of 3 biological replicates using an Illumina HiSeq 2500
Publication Title
Transcriptomic analysis of the hippocampus from six inbred strains of mice suggests a basis for sex-specific susceptibility and severity of neurological disorders.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 72 Downloadable Samples
- IlluminaHiSeq2500
Description
The developmental transition to motherhood requires gene expression changes that alter the brain to prepare and drive the female to perform maternal behaviors. Furthermore, it is expected that the many physiological changes accompanying pregnancy and postpartum stages will impact brain gene expression patterns. To understand how extensive these gene expression changes are, we examined the global transcriptional response broadly, by examining four different brain regions: hypothalamus, hippocampus, neocortex, and cerebellum. Further, to understand the time course of these changes we performed RNA-sequencing analyses on mRNA derived from virgin females, two pregnancy time points and three postpartum time points. We find that each brain region and time point shows a unique molecular signature, with only 49 genes differentially expressed in all four regions, across the time points. Additionally, several genes previously implicated in underlying postpartum depression change expression. This study serves as a comprehensive atlas of gene expression changes in the maternal brain in the cerebellum, hippocampus, hypothalamus, and neocortex. At each of the time points analyzed, all four brain regions show extensive changes, suggesting that pregnancy, parturition, and postpartum maternal experience substantially impacts diverse brain regions. Overall design: Libraries were prepared from three independent biological replicates, mRNA for each biological replicate was derived from a single mouse brain, with each mouse brain being used to collect all four brain regions.
Publication Title
An Examination of Dynamic Gene Expression Changes in the Mouse Brain During Pregnancy and the Postpartum Period.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Obesity is strongly associated with the metabolic syndrome, a compilation of risk factors that predispose individuals to the development of cardiometabolic disease (CMD), i.e. cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM). Controlling or preventing the worldwide epidemic of metabolic syndrome requires novel interventions to address this substantial health challenge. The objective of this study was the identification of potential new targets for the simultaneous prevention and treatment of insulin resistance and atherosclerosis, conditions that underlie T2DM and CVD, respectively. Therefore, we used an unbiased bioinformatics approach to identify molecules that are upregulated in both conditions by combining data from two microarray experiments and two meta-analyses. In the microarray experiments we compared gene expression in white adipose tissue (WAT) of obese mice as well as aortae of obese and atherosclerotic mice to respective lean controls. Furthermore, we performed a meta-analysis of published microarrays investigating atherosclerotic vessels and included a published meta-analysis on T2DM into our analyses. We obtained a pool of thirty-four genes that were upregulated in 3 out of the 4 underlying databases. These included well-known as well as novel crucial molecules for treatment of T2DM and CVD. Macrophage metalloelastase 12 (MMP12) was found highly ranked in all analyses and, therefore, chosen for further validation. Analyses of visceral and subcutaneous white adipose tissue from obese compared to lean mice and humans convincingly confirmed the up-regulation of MMP12 in obesity at mRNA, protein and, of note, activity levels. In conclusion, by this unbiased approach an interesting pool of potential molecular targets or biomarkers for treatment and prevention of CMD was identified with MMP12 being confirmed on multiple levels.
Publication Title
Identification of matrix metalloproteinase-12 as a candidate molecule for prevention and treatment of cardiometabolic disease.
Sample Metadata Fields
Specimen part
View Samples