Purpose: Selecting muscle-invasive bladder cancer patients for adjuvant therapy is currently based on clinical variables with limited power. We hypothesized that genomic-based signatures can outperform clinical models to identify patients at higher risk. Method:Transcriptome-wide expression profiles were generated using 1.4 million feature-arrays on archival tumors from 225 patients who underwent radical cystectomy and had muscle-invasive and/or node-positive bladder cancer. A 15-feature GC was developed on the discovery set with area under curve (AUC) of 0.77 in the validation set.
Discovery and validation of novel expression signature for postcystectomy recurrence in high-risk bladder cancer.
Specimen part
View SamplesBACKGROUND: Due to their varied outcomes, men with biochemical recurrence (BCR) following radical prostatectomy (RP) present a management dilemma. Here, we evaluate Decipher, a genomic classifier (GC), for its ability to predict metastasis following BCR.
A genomic classifier predicting metastatic disease progression in men with biochemical recurrence after prostatectomy.
Specimen part
View SamplesPurpose: Clinicopathologic features and biochemical recurrence are sensitive, but not specific, predictors of metastatic disease and lethal prostate cancer. We hypothesize that a genomic expression signature detected in the primary tumor represents true biological potential of aggressive disease and provides improved prediction of early prostate cancer metastasis.
Discovery and validation of a prostate cancer genomic classifier that predicts early metastasis following radical prostatectomy.
No sample metadata fields
View SamplesPurpose: Patients with locally advanced prostate cancer after radical prostatectomy are candidates for secondary therapy. However, this higher risk population is heterogeneous. Many cases do not metastasize even when conservatively managed. Given the limited specificity of pathological features to predict metastasis, newer risk prediction models are needed. We report a validation study of a genomic classifier that predicts metastasis after radical prostatectomy in a high risk population. Method:A case-cohort design was used to sample 1,010 patients after radical prostatectomy at high risk for recurrence who were treated from 2000 to 2006. Patients had preoperative prostate specific antigen greater than 20 ng/ml, Gleason 8 or greater, pT3b or a Mayo Clinic nomogram score of 10 or greater. Patients with metastasis at diagnosis or any prior treatment for prostate cancer were excluded from analysis. A 20% random sampling created a subcohort that included all patients with metastasis. We generated 22-marker genomic classifier scores for 235 patients with available genomic data. ROC and decision curves, competing risk and weighted regression models were used to assess genomic classifier performance.
Validation of a genomic classifier that predicts metastasis following radical prostatectomy in an at risk patient population.
Age
View SamplesRadiation is an established cause of thyroid cancer and growing evidence supports a role for H2O2 in spontaneous thyroid carcinogenesis. Little is known about the molecular programs activated by these agents in thyroid cells. We profiled the DNA damage response and cell death induced by -radiation (0.15Gy) and H2O2 (0.00250.3mM) in primary human thyroid cells and T-cells. While the two cell types had more comparable radiation responses, 3- to 10-fold more H2O2 was needed to induce detectable DNA damage in thyrocytes. At H2O2 and radiation doses incurring double-strand breaks (DSB), cell death occurred after 24hrs in T-cells, but not in thyrocytes. We next prepared thyroid and T-cells primary cultures from 8 donors operated for non-cancerous pathologies and profiled their genome-wide transcriptional response 4hr after: 1) exposure to 1 Gy radiation, 2) treatment with H2O2, or 3) no treatment. Two H2O2 doses were investigated, calibrated in each cell type as to elicit levels of single- and double-strand breaks equivalent to 1 Gy -radiation. The transcriptional responses of thyrocyte and T-cells to radiation were similar, involving DNA repair and cell death genes. In addition to this transcriptional program, H2O2 also upregulated antioxidant genes in thyrocytes, including glutathione peroxidases (GPx) at the DSB-inducing dose. By contrast, a transcriptional storm involving thousands of genes was raised in T-cells. Finally, we showed that GPx inhibition reduced the DNA damaging effect of H2O2 in thyrocytes. We conjecture that defects of anti- H2O2 protection could promote spontaneous thyroid cancers.
Comparative analysis of the thyrocytes and T cells: responses to H2O2 and radiation reveals an H2O2-induced antioxidant transcriptional program in thyrocytes.
Sex, Age, Treatment, Subject
View SamplesIn order to identify biologically relevant tumor markers, and novel therapeutic target we have compared the tumor gene expression profiles of long (OS>=24 months,n=14) and short (OS <=7months, n=11) survival patients. Then we conducted Kaplan-Meier survival analysis using all the 50 samples listed here. The Affymetrix gene-expression data of these 50 samples were also included in the earlier submission by us as GEO accession number GSE62452.
Endothelial Nitric Oxide Synthase Traffic Inducer (NOSTRIN) is a Negative Regulator of Disease Aggressiveness in Pancreatic Cancer.
Specimen part
View SamplesIn order to identify biologically relevant tumor markers with prognostic significance, we set out to analyze gene expression profiling of tumor and adjacent non-tumor tissues from PDAC cases.
DPEP1 inhibits tumor cell invasiveness, enhances chemosensitivity and predicts clinical outcome in pancreatic ductal adenocarcinoma.
Specimen part
View SamplesIn order to identify biologically relevant tumor markers , we analyzed gene expression profiling of tumor and adjacent non-tumor tissues from PDAC cases. We compared the microarray gene-expression profiles of MIF-high and MIF low expressing tumors as detrmined by qRT-PCR. Affymetrix gene-expression analysis was done in two sets. Affymetrix data from sample number 1-90 were earlier submited by us as GEO accession#: GSE28735. The batch effect between the two sets of data was removed using Partek Genomic Suite and this normalized data was submitted to GEO in this submission. All the analysis was performed using the merged data set.
A Novel MIF Signaling Pathway Drives the Malignant Character of Pancreatic Cancer by Targeting NR3C2.
Specimen part
View SamplesGenome-wide alternative splice analysis of RNA from lupus and its severe form lupus nephritis
Genome-wide peripheral blood transcriptome analysis of Arab female lupus and lupus nephritis.
Sex, Specimen part, Disease stage
View SamplesWe performed single-cell mRNA-Seq on wild-type mouse keratinocytes co-cultured with keratinocytes in which beta-catenin was activated. We identified seven distinct cell states in cultures that had not been exposed to the beta-catenin stimulus. Using temporal single-cell analysis we reconstruct the cell fate changes induced by neighbor Wnt activation. Gene expression heterogeneity was reduced in neighboring cells and this effect was most dramatic for protein synthesis associated genes. The changes in gene expression were accompanied by a shift from a quiescent to a more proliferative stem cell state. By integrating imaging and reconstructed sequential gene expression changes during the state transition we identified transcription factors, including Smad4 and Bcl3, that were responsible for effecting the transition in a contact-dependent manner. Our data indicate that non cell autonomous Wnt/beta-catenin signaling decreases transcriptional heterogeneity and further our understanding of how epidermal Wnt signaling orchestrates regeneration and self-renewal. Overall design: Comparison of cells exposed to Wnt activated neighbors versus unactivated.
Epidermal Wnt signalling regulates transcriptome heterogeneity and proliferative fate in neighbouring cells.
Specimen part, Treatment, Subject
View Samples