Morbidity and mortality associated with retinoblastoma have decreased drastically in recent decades, in large part due to better prediction of high-risk disease and appropriate treatment stratification. High-risk histopathologic features and severe anaplasia both predict the need for more aggressive treatment; however, not all centers are able to easily assess tumor samples for degree of anaplasia. Instead, identification of genetic signatures able to distinguish among anaplastic grades and thus predict high versus low risk retinoblastoma would facilitate appropriate risk stratification in a wider patient population. A better understanding of genes dysregulated in anaplasia would also yield valuable insights into pathways underlying the development of more severe retinoblastoma. Here, we present the histopathologic and gene expression analysis of 28 retinoblastoma cases using microarray analysis. Tumors of differing anaplastic grade show clear differential gene expression, with significant dysregulation of unique genes and pathways in severe anaplasia. Photoreceptor and nucleoporin expression in particular are identified as highly dysregulated in severe anaplasia and suggest particular cellular processes contributing to the development of increased retinoblastoma severity. A limited set of highly differentially expressed genes are also able to accurately predict severe anaplasia in our dataset. Together, these data contribute to the understanding of the development of anaplasia and facilitate the identification of genetic markers of high-risk retinoblastoma.
Distinct Gene Expression Profiles Define Anaplastic Grade in Retinoblastoma.
Specimen part
View SamplesHuman conjunctival cell lines are useful tools for modeling ocular surface disease and evaluation of ocular drugs. Here we demonstrate that the IOBA-NHC and the ChWK conjunctival epithelial cell lines show, using an unbiased gene microarray approach, unique gene expression signatures that differ from primary conjunctival epithelial cells (PCEC) and conjunctival tissue. Globally, the expression profile obtained with the Affymetrix U133A chip (>22000 genes) from PCEC was clustered more closely to conjunctival tissue than either of the 2 cell lines. However, when restricted to Gene Ontology sub-categories: cellular defense, viral replication/cycling, antigen presentation, anti-oxidant pathways and ubiquitin ligase complex, the cell lines correlated reasonably well to PCEC (r > 0.70). In the category response to inflammation, correlation of cell lines to PCEC was poor (r = -0.012 and 0.041 for IOBA-NHC and ChWK respectively). In general, the expression profile in IOBA-NHC cells was better correlated to PCEC than the ChWK cells. This was statistically significant (p<0.05) when one considers all the genes on the chip, or for proteins in the extracellular region, response to wounding, stress, lipid, protein and organic acid metabolism, development and differentiation. Our results are useful for the choice of conjunctival cell lines, if necessary, in future experiments, to increase validity of extrapolation to clinical scenarios.
Comparison of gene expression profiles of conjunctival cell lines with primary cultured conjunctival epithelial cells and human conjunctival tissue.
No sample metadata fields
View SamplesTranscriptome-wide investigation of mRNA and circular RNA in miR-184 and mutant miR-184(r.57c>u) treatment human lens epithelial cells
No associated publication
Sex, Specimen part, Cell line
View SamplesHuman Lens Epithelial Cells treated by NC
No associated publication
Sex, Specimen part, Cell line
View SamplesThis study aimed to identify genes that are linked with optineurin expression using a combined siRNA-microarray approach
Identification of genes that are linked with optineurin expression using a combined RNAi--microarray approach.
No sample metadata fields
View SamplesWe differentiated hESC into retinal pigment epithelial cells using two methods (three-dimensional culture and spontaneous differentiation methods). We investigated which kind of RPE cells derived from hESC showed similar gene expression patterns to those of human fetal native RPE.
No associated publication
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Systems Analysis of Immunity to Influenza Vaccination across Multiple Years and in Diverse Populations Reveals Shared Molecular Signatures.
Specimen part, Subject, Time
View SamplesWe applied a systems biology approach to study immune responses in subjects receiving 3 consecutive immunizations with RTS,S/AS01 (RRR), or in those receiving 2 immunizations of RTS,S/AS01, following a primary immunization with adenoviral Ad35 (ARR) vector expressing circumsporozoite protein.
Systems analysis of protective immune responses to RTS,S malaria vaccination in humans.
Specimen part, Disease stage, Subject, Time
View SamplesThe goal of this study is to characterize the human immune responses to the live attenuated Herpes zoster vaccine Zostavax, to understand the molecular and cellular mechanisms that lead to antibody production and T cell induction, and to understand the difference between young and elderly healthy adults. The overall data collection included antigen specific assays, flow cytometric profiling of innate and adaptive cell populations, measurement of serum cytokines, and transcriptomic and metabolomics signatures. Zostavax induced robust antigen-specific antibody responses, and significant T cell responses. A number of gene pathways were upregulated after vaccination. Using our previously developed blood transcription modules, we also identified transcriptomic correlates to antibody response. Furthermore, this study revealed strong association between PBMC transcriptomics and plasma metabolomics. Integrative analysis of orthogonal datasets from metabolomics, transcriptomic and immune profiling facilitated a temporal reconstruction of Zostavax induced biological networks culminating in antibody responses , and the delineation of novel molecular correlates of vaccine immunity.
Metabolic Phenotypes of Response to Vaccination in Humans.
Sex, Age, Specimen part, Race, Subject
View SamplesSystems approaches have been used to describe molecular signatures driving immunity to influenza vaccination in humans.
Systems Analysis of Immunity to Influenza Vaccination across Multiple Years and in Diverse Populations Reveals Shared Molecular Signatures.
Specimen part, Subject, Time
View Samples