Hypoxia triggers aggressive cancer growth and contributes to chemotherapy resistance. Novel therapeutic strategies aim at targeting hypoxia activated signaling pathways. Tumor hypoxia not only affects neoplastic tumor cells but also the surrounding stroma cells. Therefore, a novel ex vivo model was established, which allows the study of hypoxia effects in fragments of non-small cell lung cancer (NSCLC) with preserved tumor microenvironment and 3D-structure. Microarray analysis identified 107 significantly regulated genes with at least two-fold expression change in hypoxic compared to normoxic fragments. However, only four genes were significantly regulated in both subtypes, adenocarcinoma and squamous cell carcinoma. The hypoxic regulation of these four genes was verified in an independent set using quantitative PCR.
Hypoxia increases membrane metallo-endopeptidase expression in a novel lung cancer ex vivo model - role of tumor stroma cells.
Specimen part, Treatment
View SamplesColorectal cancer is one of the most common cancers in the world. Histological staging is efficient but combination with molecular markers may improve tumors classification. Gene expression profiles have been defined as prognosis predictors among stage II and III tumors but their implementation in medical practice remains controversial. Stage-II tumors have been recognized as a heterogeneous group and high-risk morphologic features have been retained as justifying adjuvant chemotherapy. We propose here the investigation of clinical features and expression profiles from stage II and stage III colon carcinomas without DNA mismatch repair defect. A series of 130 colon cancer samples was retained. Expression profiles were established on oligonucleotide microarrays and processed in the R/Bioconductor environment. Hierarchical then supervised analyses were successively performed applying the data-sampling approach. A molecular signature of seven genes was found to cluster stage III tumors with an adjusted p-values lower than 10^-10. A subgroup of stage-II tumors aggregated this cluster in both series. No correlation was found between with the disease severity but the function of the discriminating genes suggests that tumors have been classified according to their putative response to adjuvant targeted or classic therapies. Further pharmacogenetic studies might document this observation.
A seven-gene signature aggregates a subgroup of stage II colon cancers with stage III.
Sex, Age, Specimen part
View SamplesAnalysis of expression profiles in stage II colon cancer according to the APC gene status
Expression Profiles in Stage II Colon Cancer According to APC Gene Status.
Sex, Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Gene expression classification of colon cancer into molecular subtypes: characterization, validation, and prognostic value.
Sex
View SamplesFrom a clinical and molecular perspective, colon cancer (CC) is a heterogeneous disease but to date no classification based on high-density transcriptome data has been established. The aim of this study was to build up a robust molecular classification ofmRNA expression profiles (Affymetrix U133Plus2) ofa large series of 443 CC and 19 non-tumoral colorectal mucosas, and to validate it on an independent serie of 123 CC and 906 public dataset.We identified and validated six molecular subtypes in this large cohort as a combination of multiple molecular processes that complement current disease stratification based on clinicopathological variables and molecular markers. The biological relevance of these subtypes was consolidated by significant differences in survival. These insights open new perspectives for improving prognostic models and targeted therapies.
Gene expression classification of colon cancer into molecular subtypes: characterization, validation, and prognostic value.
Sex
View SamplesPancreatic ductal adenocarcinoma (PDA) carries a dismal prognosis and current treatments are only modestly effective. We present evidence that this variation is caused in part by recurrent, pervasive molecular differences between tumors. mRNA expression profiles measured using microdissected PDA clinical samples reveal three dominant subtypes of disease; epithelial, mesenchymal and acinar-like. The classical and quasi-mesenchymal subtypes are observed in human and mouse PDA cell lines. Importantly, responses to cytotoxics and KRAS depletion in human PDA cell lines differ substantially between subtypes, and in opposing directions. Integrated genomics implicate and functional studies support overexpression of the trancription factor GATA6 as a driver of the epithelial subtype. These results provide a molecular framework for evaluating the prospects of personalized treatment in PDA.
Subtypes of pancreatic ductal adenocarcinoma and their differing responses to therapy.
Specimen part, Cell line
View SamplesTo identify targets of PDGFRb signaling and potentially new markers for pericyte activation, we used microarray analysis to compare gene expression in control and mutant pericytes expressing a constitutively active PDGFRb.
PDGFRβ signaling regulates mural cell plasticity and inhibits fat development.
Specimen part
View SamplesThe conserved Snf1/AMPK (AMP-activated protein Kinase) family is one of the central components in nutrient sensing and regulation of carbon metabolism in eukaryotes. It is also involved in several other processes such as stress resistance, invasive growth and ageing. Snf1 kinase is composed of a catalytic -subunit Snf1, a regulatory -subunit Snf4 and one of three possible -subunits, Sip1, Sip2 or Gal83. We used a systematic approach to study the role of the three -subunits by analyzing all 7 possible combinations of -subunit deletions together with the reference strain.
The beta-subunits of the Snf1 kinase in Saccharomyces cerevisiae, Gal83 and Sip2, but not Sip1, are redundant in glucose derepression and regulation of sterol biosynthesis.
No sample metadata fields
View SamplesBackground & Aims: Genome-wide gene expression (GWGE) profiles of mucosal colonic biopsies have suggested the existence of a continuous inflammatory state in quiescent ulcerative colitis (UC). The aim of this study was to use DNA microarray-based GWGE profiling of mucosal colonic biopsies and isolated colonocytes from UC patients and controls in order to identify the cell types responsible for the continuous inflammatory state. Methods: Adjacent mucosal colonic biopsies were obtained endoscopically from the descending colon in patients with active UC (n=8), quiescent UC (n=9), and with irritable bowel syndrome (controls, n=10). After isolation of colonocytes and subsequent extraction of total RNA, GWGE data were acquired using Human Genome U133 Plus 2.0 GeneChip Array (Affymetrix, Santa Clara, CA). Data analysis was carried out by principal component analysis and projection to latent structure-discriminant analysis using the SIMCA-P11 software (Umetrics, Ume, Sweden). Results: A clear separation between active UC, quiescent UC and control biopsies were found, whereas the model for the colonocytes was unable to distinguish between quiescent UC and controls. The differentiation between quiescent UC and control biopsies was governed by unique profiles containing gene expressions with significant fold changes. These primarily belonged to the family of homeostatic chemokines revealing a plausible explanation to the abnormal regulated innate immune response seen in patients with UC. Conclusion: This study has demonstrated the presence of a continuous inflammatory state in quiescent UC, which seems to reflect an altered gene expression profile of lamina propria cells.
Genome-wide gene expression analysis of mucosal colonic biopsies and isolated colonocytes suggests a continuous inflammatory state in the lamina propria of patients with quiescent ulcerative colitis.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Impaired tissue regeneration corresponds with altered expression of developmental genes that persists in the metabolic memory state of diabetic zebrafish.
Specimen part, Disease, Disease stage
View Samples