Stromal and epithelial changes in breast cancer following endocrine treatment
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Narges Azadbakht
PROVIDER: E-GEOD-58598 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Background: Human papillomavirus has been shown to have a causal role in the development of head and neck squamous cell carcinoma and represents a distinct and well-defined pathology. While HPV-positive HNSCC is associated with a better response to treatment and prognosis, a subset of patients do not respond favorably to current standard of care thus suffering unnecessary morbidity and delay to receive effective therapy. Methods: RNA from nineteen patients with HPV-positive HNSCC was subjected to gene expression analysis using Affymetrix microarrays. HPV-status was confirmed by detection of HPV16 E7 with RT-PCR. Results: In addition to specific genetic biomarkers (including LCE3D, KRTDAP, HMOX1, KRT19, MDK, TSPAN1), differentially expressed genes were highly represented in the cell processes of genomic stability, cell cycle, and DNA damage. Conclusions: This pilot study suggests possible biomarkers that predict response to chemoradiation therapy. These data can potentially lead to an assay that can be used clinically to predict HPV-positive HNSCC patients that will not benefit from chemoradiation, thus helping clinicians to lower morbidity and get selected patients to surgery faster. HPV-positive head and neck squamous cell carcinoma (HNSCC) has a good prognosis with a large percentage of patients responding to therapy. However, a certain percentage of patients do not respond. Gene expression data from Affymetrix Human Exon 1.0ST microarrays was utilized to compare patients that responded to therapy with those that did not respond.
2014-12-19 | E-GEOD-40020 | biostudies-arrayexpress
Project description:Purpose: Due to the rarity of Merkel Cell Carcinoma (MCC), prospective clinical trials have not been practical. This study seeks to identify biomarkers to differentiate between patients with a good and poor prognosis. Methods: Patients were stratified into good, moderate or poor prognosis. Merkel cell carcinoma (MCC) patients were stratified into one of three groups based upon status 24 months following treatment. Poor prognosis patients either presented with or progressed to distant metastasis. Patients with favorable prognosis had local disease presentation with no subsequent recurrence or nodal disease at presentation with no progression during follow-up of longer than 24 months. Moderate prognosis had recurrent local disease, development of nodal metastasis, or nodal disease at presentation with no progression during follow-up of fewer than 24 months. Using ArcturusXT Laser Capture Microdissection (Molecular Devices), tumor cells were isolated from the specific areas of interest. The captured tumor tissue was subjected to RNA extraction using the Invitrogen PureLinkM-bM-^DM-" FFPE RNA Isolation Kit. The extracted RNA was analyzed for integrity with the Agilent Bioanalyzer then amplified and hybridized to Affymetrix GeneChip Human Exon 1.0 ST arrays using the NuGEN WT- OvationM-bM-^DM-" FFPE System. Results: A total of 191 genes showed significant differential expression (pM-bM-^IM-$0.05 and 1.5-fold cutoff) between the different between the good and poor prognosis groups. Keratin 20 (KRT20) and Neurofilament protein (NEFM) have been identified in previous studies as proteins of interest in MCC. Our study showed these genes to be significantly upregulated in patients with a poor prognosis. Of interest, phospholipase A2, group X was upregulated in poor responders. Phospholipases liberate arachidonic acid from cellular membranes which can be metabolized to eicosanoids through three major pathways: the cyclooxygenase (COX), the lipoxygenase (LOX) and the cytochrome P450 monooxygenase pathways. This pathway has been implicated in several cancers. Conclusions: The study identified genes with a previous association with MCC as well as some novel genes. These genes provide the basis for further research into possible biomarkers that will enable the differentiation between patients with a good and poor prognosis. Using laser capture microdissection, tumor cells of patients with a good (n=5), moderate (n=3), and poor prognosis (n=7) were isolated from paraffin embedded archival tissue of 15 patients with Merkel cell carcinoma. Affymetrix Human Exon 1.0ST microarrays were utilized to compare gene expression signatures from good and poor prognosis patients.
2014-02-20 | E-GEOD-36150 | biostudies-arrayexpress
Project description:Pediatric GIST commonly harbors a disabled succinate dehydrogenase complex (SDH), which yields tumors with highly conserved genomes but characteristic epigenomic signatures. Mysteriously, nearly half of such SDH-deficient GIST, including tumors from Carney Triad patients, lack identifiable mutations in SDH component genes and genes required for complex assembly (SDHA, SDHB, SDHC, SDHD, SDHAF, termed SDHx). Genomic sequencing coupled with DNA methylation and transcriptional profiling have exposed SDHC promoter-specific CpG island epimutation and concomitant gene silencing in the majority of SDHx-WT GIST. We performed whole genome expression profiling on 20 FFPE dSDH GIST tumors using Affymetrix U133P2 arrays which contain >54K gene target probesets. Included here were data from 7 SDHx-w.t. and 13 SDHx mutants that passed array QC.
2015-01-02 | E-GEOD-56670 | biostudies-arrayexpress
Project description:The HSC niche factor SCF is required for HSC maintenance. Using an Scf-GFP knockin mouse, we have identified a perivascular cell type in the bone marrow expressing high level of Scf. To characterize the novel Scf-GFP+ cells from the bone marrow, we performed microarray analysis on these cells. Total RNA were isolated from 3 independent, freshly aliquots of FACS sorted 5,000 SCF-GFP+ cells or whole bone marrow cells isolated from young adult mice. Purified RNA was amplified using the WT-OvationM-bM-^DM-" Pico RNA Amplification system (NuGEN Technologies). Sense strand cDNA was generated using WT-OvationM-bM-^DM-" Exon Module (NuGEN), then fragmented and labeled using the FL-OvationM-bM-^DM-" cDNA Biotin Module V2 (NuGEN). 2.5M-BM-5g of labeled cDNA were hybridized to Affymetrix Mouse Gene ST 1.0 microarrays.
2012-02-01 | E-GEOD-33158 | biostudies-arrayexpress
Project description:Glucocorticoid excess is linked to central obesity, adipose tissue insulin resistance and type 2 diabetes mellitus. The aim of our study was to investigate the effects of dexamethasone on gene expression in human subcutaneous and omental adipose tissue, in order to identify potential novel mechanisms and biomarkers for glucocorticoid-induced insulin resistance in adipose tissue. Dexamethasone changed the expression of 527 genes in both subcutaneous and omental adipose tissue. FKBP5 and CNR1 were the most responsive genes in both depots (~7-fold increase). Dexamethasone increased FKBP5 gene and protein expression in a dose-dependent manner in both depots, but FKBP5 protein levels were 10-fold higher in omental than subcutaneous adipose tissue. FKBP5 gene expression in subcutaneous adipose tissue was positively correlated with serum insulin, HOMA-IR and subcutaneous adipocyte diameter, while fold change in gene expression by dexamethasone was negatively correlated with clinical markers of insulin resistance, i.e. HbA1c, BMI, HOMA-IR and serum insulin. Only one gene, SERTM1, clearly differed in response to dexamethasone between the two depots. Dexamethasone at high concentrations, influences gene expression in both subcutaneous and omental adipose tissue in a similar pattern and promotes gene expression of FKBP5, a gene that may be implicated in glucocorticoid-induced insulin resistance. Paired human subcutaneous (sc) and omental (om) adipose tissue samples obtained from 4 non-diabetic adipose tissue donors (4 M; BMI: 20.8-27.5 Kg/m2) were incubated without (Ctr) or with dexamethasone (Dex, 3 M-NM-<M) for 24 h.
2014-08-18 | E-GEOD-42902 | biostudies-arrayexpress
Project description:Patients diagnosed with breast cancer were recruited to an important trial, the Tamoxifen Window Trial, in two series, series A during 1988-1989 and series B during 1989-1990. Some patients received tamoxifen for short windows. Clinical samples (biopsies) for this trial were collected before and after treatment. These biopsies were available as formalin-fixed paraffin-embedded (FFPE) tissue blocks. Responding patients and non-responding patients were determined by the change in the Ki67 scores. Responding patients were identified as those that had demonstrated a reduction in their Ki67 scores, and non-responding patients were identified as those in which Ki67 had not changed or had increased. The change in the percentage of Ki67 positive tumour cells was obtained by comparing the pre-treatment and post-treatment scores and calculating the difference in the scores. Laser capture microdissection (LCM) was utilised to microdissect the epithelial and stromal cells from the post-treatment breast cancer FFPE tissue sections of responding and non-responding patients. Samples obtained following LCM underwent RNA extraction and were subsequently used for gene expression profiling.
2014-07-07 | GSE58598 | GEO
Project description:Purpose: The diagnosis of high grade intraductal papillary mucinous neoplasm (IPMN) is difficult to distinguish from low grade IPMN. The aim of this study was to identify potential markers for the discrimination of high grade and invasive IPMN from low and moderate grade IPMN. Experimental Design: Laser capture microdissection was used to isolate distinct foci of low grade, moderate grade, high grade, and invasive IPMN from paraffin embedded archival tissue from 14 patients who underwent resection for IPMN. Most samples included multiple grades in the same specimen. Affymetrix Human Exon microarrays were used for gene expression analysis to compare low and moderate grade (LMD) IPMN to high grade and invasive (HgInv) IPMN. Results: When comparing samples of LMD dysplasia (n=15) to those demonstrating HgInv (n=13), 62 genes were identified as showing significant changes in expression (p≤0.05 and a 2-fold cutoff), with up-regulation of 41 in HgInv IPMN and down-regulation in 21. Changes in gene expression are associated with biological processes related to malignant behavior including cell motion, cell proliferation, response to hypoxia, and epithelial to mesenchymal transition. Hierarchical clustering analysis demonstrated the ability of these 62 differentially expressed genes to distinguish between LMD and HgInv samples. In addition, altered signaling in several TGFβ-related pathways was exhibited in the progression of IPMN to malignancy. Conclusions: This study identifies a set genes associated with the progression of IPMN to malignancy. These genes are potential markers that could be used to identify IPMN requiring surgical resection. Using laser capture microdissection, distinct foci of low (n=10), moderate (n=5), and high grade dysplasia (n=6) as well as invasive carcinoma (n=7) were isolated from paraffin embedded archival tissue of 14 patients who underwent resection for IPMN. Gene expression data from Affymetrix Human Exon 1.0ST microarrays was utilized to compare low and moderate grade IPMN to high and invasive IPMN.
2011-12-01 | E-GEOD-26647 | biostudies-arrayexpress
Project description:Background: CrohnM-bM-^@M-^Ys disease is presently an incurable inflammatory bowel disease. Fistulae are extensions of the intestinal tract that may form connections with other organs. These are a common complication of CrohnM-bM-^@M-^Ys disease affecting up to 50% of patients with the most common including perianal and rectovaginal fistulae. The dysregulated growth observed in fistulae shares several major characteristics seen in the development of tumours. These similarities include epithelial-to-mesenchymal transition (EMT), invasive cell growth, increased extracellular matrix production and remodelling, up-regulated local expression of growth factors such as IGF-1 and the down-regulation of apoptosis pathways. Although several susceptibility loci have been described within CrohnM-bM-^@M-^Ys disease there is no individual gene or mutation that identifies susceptibility or the subsequent formation of fistulae within all people. Copy-number variation (CNV) is one mechanism that may explain much of this genetic complexity. CNV may be caused by a variety of mechanisms such as cycles of chromosomal breakage/fusion/bridging that are typical within chronically inflamed tissue. Interestingly CNV shows locus-specific mutation rates between individuals higher than that of SNPs and has been associated with complex Mendelian traits including disease susceptibility. In this current study we performed array comparative genomic hybridisation (aCGH) analysis of active fistulae resected from patients as part of a previous surgical intervention. As the control for comparison we employed tissue taken from the same patient within the same surgery at an uninvolved site of the gastrointestinal tract. This matched control was employed to better investigate CNV specific to the fistula tissue of each individual avoiding complications associated with the large number of CNV present within the healthy population. Major question addressed by the work: What are the differences in genetic copy-number within localised intestinal fistula tissue of individuals with CrohnM-bM-^@M-^Ys disease compared to healthy intestinal tissue from the same individual? Samples were selected from patients presenting with CrohnM-bM-^@M-^Ys Disease fistulae at Eastern Health Department of Gastroenterology and Hepatology (Arnold Street, Box Hill, Victoria, Australia). The 8 samples used in this study were formalin-fixed paraffin-embedded (FFPE) specimens following a surgical intervention to remove fistula tissue. To focus on changes within the individual patient we used tissue taken from the same surgery at an uninvolved region of the intestine as the matched control for CNV analysis.
2014-07-01 | E-GEOD-44275 | biostudies-arrayexpress
Project description:The RUNX genes encode for transcription factors involved in development and human disease. RUNX1 and RUNX3 are frequently associated with leukemias, yet the basis for their involvement in leukemogenesis is not fully understood. Here we show that Runx1;Runx3 double knockout (DKO) mice exhibited lethal phenotypes due to bone marrow failure and myeloproliferative disorder. These contradictory clinical manifestations are reminiscent of human inherited bone marrow failure syndromes like Fanconi anemia (FA), caused by defective DNA repair. Indeed, Runx1;Runx3 DKO cells showed mitomycin C hypersensitivity, due to impairment of monoubiquitinated-FANCD2 recruitment to DNA damage foci, although FANCD2 monoubiquitination in the FA pathway was unaffected. RUNX1 and RUNX3 interact with FANCD2 independent of CBFM-NM-2, suggesting non-transcriptional role for RUNX in DNA repair. These findings suggest that RUNX dysfunction causes DNA repair defect, besides transcriptional misregulation, and promotes development of leukemias and other cancers. 6 mice were analyzed in this study. 3 Runx1;Runx3 double knockout cKit+Sca1+Lin- hematopoietic stem/progenitor cells were compared with their wild type littermate controls. RNA was isolated from 3 independent Runx1;Runx3 WT KSL samples, each pooled from 3 Runx1;Runx3 WT mice, and 3 independent Runx1;Runx3 DKO KSL samples, using the RNeasy Micro Kit (QIAgen). RNA integrity and quantity was assessed using the Agilent 2000 Bioanalyzer system. 3 M-NM-<g to 5 M-NM-<g RNA was processed using WT-Ovation Pico RNA Amplification System (NuGEN) paired with the WT-Ovation Exon Module and FL-Ovation cDNA Biotin Module (NuGEN). A detailed protocol in the userM-bM-^@M-^Ys guide kit was used without modification. cDNA were prepared for hybridization on GeneChip Mouse Gene 1.0 ST Arrays (Affymetrix) according to the instructions in GeneChip Hybridization Wash and Stain Kit for ST arrays (Affymetrix). Microarray hybridization, scanning and preliminary MAS 5.0 normalizations were completed at the A*STAR Biopolis Shared Facilities (BSF).
2014-08-26 | E-GEOD-51107 | biostudies-arrayexpress
Project description:Objective: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS), characterized by a global increasing incidence driven by relapsing-remitting disease in females. p38 MAP kinase (MAPK) has been described as a key regulator of inflammatory responses in autoimmunity, but its role in the sexual dimorphism in MS or MS models remains unexplored. Methods: Toward this end, we used experimental autoimmune encephalomyelitis (EAE), the principal animal model of MS, combined with pharmacologic and genetic inhibition of p38 MAPK activity and transcriptomic analyses. Results: Pharmacologic inhibition of p38 MAPK selectively ameliorated EAE in female mice. Conditional deletion studies demonstrated that p38M-NM-1 signaling in macrophages/myeloid cells, but not T cells or dendritic cells, recapitulated this sexual dimorphism. Analysis of CNS inflammatory infiltrates showed that female, but not male mice lacking p38M-NM-1 in myeloid cells exhibited reduced immune cell activation compared with controls, while peripheral T cell priming was unaffected in both sexes. Transcriptomic analyses of myeloid cells revealed differences in p38M-NM-1-controlled transcripts comprising female- and male-specific gene modules, with greater p38M-NM-1 dependence of pro-inflammatory gene expression in females. Interpretation: Our findings demonstrate a key role for p38M-NM-1 in myeloid cells in CNS autoimmunity and uncover important molecular mechanisms underlying sex differences in disease pathogenesis. Taken together, our results suggest that the p38 MAPK signaling pathway represents a novel target for much needed disease modifying therapies for MS WT vs. p38alphaCKO macrophages, male vs. female
2013-10-29 | E-GEOD-51707 | biostudies-arrayexpress