Expression data from Drosophila tumor models
Ontology highlight
ABSTRACT:
ORGANISM(S): Drosophila melanogaster
PROVIDER: GSE95613 | GEO | 2018/12/21
REPOSITORIES: GEO
Similar Datasets
Project description:Prostate tumors are complex entities composed of malignant cells mixed and interacting with nonmalignant cells. However, molecular analyses by standard gene expression profiling are limited because spatial information and nontumor cell types are lost in sample preparation. We scored 88 prostate specimens for relative content of tumor, benign hyperplastic epithelium, stroma, and dilated cystic glands. The proportions of these cell types were then linked in silico to gene expression levels determined by microarray analysis, revealing unique cell-specific profiles. Gene expression differences for malignant and nonmalignant epithelial cells (tumor versus benign hyperplastic epithelium) could be identified without being confounded by contributions from stroma that dominate many samples or sacrificing possible paracrine influences. Cell-specific expression of selected genes was validated by immunohistochemistry and quantitative PCR. The results provide patterns of gene expression for these three lineages with relevance to pathogenetic, diagnostic, and therapeutic considerations. merco-00121 Assay Type: Gene Expression Provider: Affymetrix Array Designs: HG_U95Av2 Organism: Homo sapiens (ncbitax) Material Types: whole_orrganism, synthetic_RNA, organism_part, total_RNA Disease States: Normal, Prostate Cancer
2016-06-02 | E-GEOD-82132 | biostudies-arrayexpress
Project description:Prostate tumors are complex entities composed of malignant cells mixed and interacting with nonmalignant cells. However, molecular analyses by standard gene expression profiling are limited because spatial information and nontumor cell types are lost in sample preparation. We scored 88 prostate specimens for relative content of tumor, benign hyperplastic epithelium, stroma, and dilated cystic glands. The proportions of these cell types were then linked in silico to gene expression levels determined by microarray analysis, revealing unique cell-specific profiles. Gene expression differences for malignant and nonmalignant epithelial cells (tumor versus benign hyperplastic epithelium) could be identified without being confounded by contributions from stroma that dominate many samples or sacrificing possible paracrine influences. Cell-specific expression of selected genes was validated by immunohistochemistry and quantitative PCR. The results provide patterns of gene expression for these three lineages with relevance to pathogenetic, diagnostic, and therapeutic considerations.
2016-06-02 | GSE82132 | GEO
Project description:MicroRNA (miRNA) expression profiles were generated from prostate epithelial sub-populations, enriched from patient-derived benign prostatic hyperplasia (BPH, n=5), Gleason 7 treatment naïve prostate cancer (PCa, n=5) and castration-resistant prostate cancer (CRPC, n=3). Microarray expression was validated in an independent patient cohort (n=10). The analyses show that miRNA expression in epithelial sub-populations (e.g. stem cells) clustered together, irrespective of pathological status. We also discovered concordance between the miRNA expression profiles of unfractioned CRPCs, human embryonic stem cells (SCs), and prostate epithelial SCs (both, benign and malignant). miR-548c-3p was chosen as a candidate miRNA from this group to explore its utility as a CRPC biomarker and/or therapeutic target. Overexpression of miR-548c-3p was confirmed in cancer SCs (8-fold, p<0.05) and unfractionated CRPCs (1.8-fold, p<0.05). Enforced overexpression of miR-548c-3p in differentiated cells induced stem-like properties (p 0.01) and radioresistance (p<0.01). Re-analyses of published studies further revealed that miR-548c-3p is significantly overexpressed in CRPC (p<0.05) and is associated with poor recurrence-free survival (p<0.05), suggesting that miR-548c-3p is a functional biomarker for prostate cancer aggressiveness. Our results validate the prognostic and therapeutic relevance of miRNAs for advanced prostate cancer management, whilst demonstrating that resolving cell-type and differentiation-specific differences is essential to obtain clinical relevant miRNA expression profiles. There are 42 samples in total: 15 benign prostatic hyperplasia, 15 prostate cancers, 9 treatment-resistant prostate cancer. There are stem cells, transit amplifying cells and committed basal cells dissected from each sample. Three PrEC samples of each three cell types can be used as reference.
2016-07-03 | E-GEOD-59156 | biostudies-arrayexpress
Project description:The capacity of tumor cells to maintain continual overgrowth potential has been linked to the commandeering of normal self-renewal pathways. Using an epithelial cancer model in Drosophila we carried out an overexpression screen for oncogenes capable of cooperating with the loss of the epithelial apico-basal cell polarity regulator, scribbled, and identified the cell fate regulator, Abrupt, a BTB-zinc finger protein. Abrupt overexpression alone is insufficient to transform cells, but in cooperation with scrib loss of function, Abrupt promotes the formation of massive tumors in the eye/antennal disc. The steroid hormone receptor coactivator, Taiman (SRC3/AIB1), is known to associate with Abrupt, and Taiman overexpression also drives tumor formation in cooperation with the loss of Scribbled. Expression arrays and ChIP-Seq indicates that Abrupt overexpression represses a large number of genes, including steroid hormone-response genes and multiple cell fate regulators, thereby maintaining cells within an epithelial progenitor-like state. The progenitor-like state is characterised by the failure to express the conserved Eyes absent/Dachshund regulatory complex in the eye disc, and in the antennal disc by the failure to express cell fate regulators that define the temporal elaboration of the appendage along the proximo-distal axis downstream of Distalless. Loss of scribbled promotes cooperation with Abrupt through impaired Hippo signaling, which is required and sufficient for cooperative overgrowth with Abrupt, and JNK signaling, which is required for tumor cell migration/invasion but not overgrowth. These results thus identify a novel cooperating oncogene, mammalian family members of which are also known oncogenes, and demonstrate that epithelial tumors in Drosophila can be characterised by the maintenance of a progenitor-like state. ChIP-Seq of Abrupt, ChIP-Seq of Abrupt (scrib-), Input, Input (scrib-)
2013-08-15 | E-GEOD-42928 | biostudies-arrayexpress
Project description:ST profiles reveals the alterations in epithelial cells in Benign Prostatic Hyperplasia.
2024-05-01 | GSE242249 | GEO
Project description:To accurately identify gene expression alterations that differentiate neoplastic from normal prostate epithelium using an approach that avoids contamination by unwanted cellular components and is not compromised by acute gene expression changes associated with tumor devascularization and resulting ischemia. Approximately 3,000 neoplastic and benign prostate epithelial cells were isolated using laser capture microdissection from snap-frozen prostate biopsy specimens provided by 31 patients who subsequently participated in a clinical trial of preoperative chemotherapy. To eliminate potential dye bias, we randomly alternated Cy3 and Cy5 labeling to neoplastic and benign epithelium across 31 samples. Labeled cDNA probes were hybridized in a head-to-head fashion, normal versus neoplastic from the same individual, to custom-made microarrays composed of 6,200 clones derived from the Prostate Expression Database.
2012-08-24 | E-GEOD-40373 | biostudies-arrayexpress
Project description:Though expression of the homeobox transcription factor Nanog is generally restricted to pluripotent cells and early germ cells, recent reports have found that Nanog is re-expressed in somatic and germ cell tumors associated with poor differentiation and aggressive disease progression. To elucidate its oncogenic properties, a modified Tet-On system was utilised to generate Nanog-inducible mice. By dexamethasone and doxycycline injection, similar Nanog expression levels as in wild-type embryonic stem cells were obtained in all major organs except for brain. Ectopic Nanog expression resulted in intestinal and colonic epithelium hyperplasia-intestinal villi had doubled in length and hyperplastic epithelium outgrowths were seen after 7 days. The tumor suppressor gene Cdx2 was downregulated at onset of Nanog expression, suggesting that crosstalk between Nanog and Cdx2 is conserved from early embryo development to adulthood. Although the mice died before they could form tumors, Cdx2 repression and intestinal hyperplasia links Nanog to tumor initiation. 8 samples were analyzed. Intestine-: Mouse intestine cells without Nanog overexpression, 2 biological rep Intestine+: Mouse intestine cells with Nanog overexpression, 2 biological rep Colon-: Mouse colon cells without Nanog overexpression, 2 biological rep Colon+: Mouse colon cells with Nanog overexpression, 2 biological rep
2014-08-11 | E-GEOD-31413 | biostudies-arrayexpress
Project description:Tissue of the breast is heterogeneous, consisting of a variety of cell types and connective tissue. This heterogeneity is also present in breast tumors and will complicate proteomic analysis, as it is not always clear whether a signal originates from the stromal environment, from normal epithelial or tumor cells. Here we microdissected a variety of cell types and stroma from benign and malignant breast tissues. We compared proteomic differences between these tissues, both from cells of epithelial origin and the stromal environment. Differences in protein abundances corresponded with several hallmarks of cancer, including loss of cell adhesion, transformation to a migratory phenotype, and enhanced energy metabolism. Furthermore, despite enriching for (tumor) epithelial cells, many changes to the extracellular matrix were detected in microdissected cells of epithelial origin. The stromal compartment was heterogeneous and richer in the number of fibroblast and immune cells in malignant sections, compared to benign tissue sections. Although this heterogeneity complicated detection of differentially abundant proteins, several markers were exclusively detected in stroma. However, as heterogeneity in the stroma is more difficult to be reduced through microdissection, comparative analysis was most informative in microdissected cells of epithelial origin, and provided a relatively complete picture of malignant transformations.
2017-01-11 | PXD003632 | Pride
Project description:The histopathological and molecular heterogeneity of prostate cancer and the limited availability of human tumor tissue make unraveling the mechanisms of prostate carcinogenesis a challenging task. Our goal was to develop an ex vivo model that could be reliably utilized to define a prognostic signature based on gene expression profiling of cell cultures that maintained the tumor phenotype. To this end, we derived epithelial cultures from tissue explanted from 59 patients undergoing radical prostatectomy or cistoprostatectomy because of Prostate Benign Hyperplasia/Prostate Cancer or Bladder Carcinoma. Patient selection criteria were absence of hormonal neo-adjuvant treatment before surgery and diagnosis of clinically localized disease. Using this unique experimental material we analyzed expression of 22.500 transcripts on the Affymetrix Human U133A Gene Chips platform. Cultures from normal/hyperplastic tissues with a prevalent luminal phenotype, and from normal prostate epithelial tissue with basal phenotype (PrEC) served as controls.,We have established a large number of prostate primary cultures highly enriched in the secretory phenotype. From them we derived an epithelial-restricted transcriptional signature that: 1) differentiated normal from tumor cells; and 2) clearly separated cancer derived lines into two distinct groups which correlated with indolent and aggressive clinical behavior of the disease. ,Our findings provide:1) a method to expand human primary prostate carcinoma cells with a luminal phenotype; 2) a powerful experimental model to study primary prostate cancer biology; and 3) a novel means to characterize these tumors from a molecular genetic standpoint for prognostic and/or predictive purposes.
2007-06-30 | E-GEOD-3868 | biostudies-arrayexpress
Project description:Intra-tumor heterogeneity (ITH) has been studied at the morphologic, genomic, and transcriptomic level, but not proteomic level. Recent advances in mass spectrometric (MS) proteome quantification techniques, exemplified by SWATH-MS, a massively parallel targeting method, now also support precise quantitative proteomic comparisons across multiple samples, thus identifying molecular and implied functional differences. Here we used SWATH-MS to analyze the proteome profiles of a set of fresh-frozen prostate tissue samples derived from radical prostatectomy specimens. A high confidence set of 1,906 proteins were consistently quantified across 60 biopsy-level tissue samples from three prostatectomy patients, each consisting of 1.0 mm punch biopsies from histologically malignant (acinar and ductal adenocarcinoma) and matching benign prostatic hyperplasia tissues. The quantitative protein profiles allowed independent quantification of the degree of intra-tumor heterogeneity for each protein in benign and malignant tissues. We found that while majority of the proteins showed comparably low intra-tumor variability, 122 proteins were highly variable in malignant and/or matching benign tissues. We observed that proteins that varied between patients or tissue types also tended to be highly variable within prostate tissues, suggesting that these variability patterns will be a critical selection criterion in future protein biomarker studies. The data also permitted investigation of the heterogeneity of multiple biochemical pathways. The high variability of several of the pathways, including Glypican-1 network, alpha-linolenic acid metabolism and celecoxib pathway, explained contradictory results regarding them in the literature. In conclusion, we demonstrated a methodology for investigating proteomic intra-tumor heterogeneity from biopsy-level tissue samples, and quantified the degree of intra-tumor heterogeneity of 1,906 proteins in prostate tumors. The method and data presented here have advanced our understanding of tumor biology and offered critical insights for future biomarker development.
2018-08-13 | PXD003497 | Pride