Previously, long-term effects on body weight and reproductive performance have been demonstrated in the chicken model of prenatal protein undernutrition by albumen removal. Introduction of such persistent alterations in phenotype suggests stable changes in gene expression. A genome-wide screening for differences in hepatic transcriptome by RNA-Seq was performed in adult Isa Brown hens (55 weeks of age). Albumen-deprived hens were created by removal of 3 ml of the albumen from fertilized eggs and replacement with saline early during embryonic development (embryonic day 1). Results were compared to mock-treated sham hens and non-treated control hens. Correlation between relative expression levels obtained from the RNA-Seq and qPCR results was very high (Pearson’s correlation coefficiënt = 0.85), confirming the validity of the RNA-Seq results. In addition, after expansion of the sample size, 7 out of 15 selected genes demonstrated the same significant gene expression differences in the qPCR as in the RNA-Seq dataset, and were thus biologically confirmed. Grouping of the differentially expressed (DE) genes according to biological functions revealed the involvement of processes such as ‘embryonic and organismal development’, ‘organ morphology’, ‘organ and tissue development’, ‘reproductive system development and function’. Molecular pathways that were altered were ‘amino acid metabolism’, ‘molecular transport’, ‘small molecule biochemistry’, ‘cell death and survival’, ‘cell-to-cell signaling and interaction’, ‘carbohydrate metabolism’ and ‘protein synthesis’. In conclusion, the present results demonstrated for the first time that prenatal protein undernutrition by albumen removal leads to long-term alterations of the hepatic transcriptome in the chicken. Overall design: 3 biological replicates per group (control, sham, albumen-deprived) were analyzed
Differential Expression of Genes and DNA Methylation associated with Prenatal Protein Undernutrition by Albumen Removal in an avian model.
Cell line, Subject
View SamplesGene expression profiles were assessed for vincristine-sensitive parental ovarian tumor cell line (SKOV3) and its highly vincristine-resistant derivative (SKVCR 2.0)
Genetic changes in the evolution of multidrug resistance for cultured human ovarian cancer cells.
No sample metadata fields
View SamplesPurpose: A number of microarray studies have reported distinct molecular profiles of breast cancers (BC): basal-like, ErbB2-like and two to three luminal-like subtypes. These were associated with different clinical outcomes. However, although the basal and the ErbB2 subtypes are repeatedly recognized, identification of estrogen receptor (ER)-positive subtypes has been inconsistent. Refinement of their molecular definition is therefore needed.
Definition of clinically distinct molecular subtypes in estrogen receptor-positive breast carcinomas through genomic grade.
Age, Disease stage
View SamplesBackground: Histologic grade in breast cancer provides clinically important prognostic information. However, 30%-60% of tumors are classified as histologic grade 2. This grade is associated with an intermediate risk of recurrence and is thus not informative for clinical decision making. We examined whether histologic grade was associated with gene expression profi les of breast cancers and whether such profi les could be used to improve histologic grading.
Gene expression profiling in breast cancer: understanding the molecular basis of histologic grade to improve prognosis.
Age, Disease stage
View SamplesBackground: 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 SamplesThis SuperSeries is composed of the SubSeries listed below.
Integrative analyses reveal signaling pathways underlying familial breast cancer susceptibility.
Specimen part
View SamplesWe obtained peripheral blood samples for women from Utah (USA) and Ontario (Canada) who had a family history of breast cancer (or did not), who carried a BRCA1/2 mutation (or did not), and who had developed breast cancer (or had not).
Integrative analyses reveal signaling pathways underlying familial breast cancer susceptibility.
Specimen part
View SamplesWe obtained peripheral blood samples for women from Utah (USA) and Ontario (Canada) who had a family history of breast cancer (or did not), who carried a BRCA1/2 mutation (or did not), and who had developed breast cancer (or had not).
Integrative analyses reveal signaling pathways underlying familial breast cancer susceptibility.
Specimen part
View SamplesPURPOSE: Validated biomarkers predictive of response/resistance to anthracyclines in breast cancer are currently lacking. The neoadjuvant TOP trial, in which patients with estrogen receptor (ER)-negative tumors were treated with anthracycline (epirubicin) monotherapy, was specifically designed to evaluate the predictive value of topoisomerase II (TOP2A) and to develop a gene expression signature to identify those patients who do not benefit from anthracyclines.
Multifactorial approach to predicting resistance to anthracyclines.
Disease stage
View SamplesThe goal was to capture the transcriptional activity due to over-expression of AKT, BAD, ERBB2, IGF1R, RAF1 and ERK1 genes.Over-expressions were validated using Western Blots. Illumina RNA-Seq technology was used to capture the downstream transcriptional activity. Reads were 101 base pairs long and single ended. An R open source package “Rsubread” was used to align and quantify the read using UCSC hg19 annotation. The integer-based gene counts were later normalized in TPM . Overall design: Profiles of gene expression, downstream of AKT, BAD, ERBB2, IGF1R, RAF1 and ERK over-expression, were generated in cells derived from breast and used to generate a gene-expression signatures.
Combating subclonal evolution of resistant cancer phenotypes.
No sample metadata fields
View Samples