TransCONFIRM gene expression analysis
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Rinath Jeselsohn
PROVIDER: E-GEOD-76040 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:gene expression analysis ussing microarray analysis of a subset of primary tumors collected from patients that participated in the CONFIRM phase III study, which randomized post menopausal patients with ER+ metastatic breast cancer to fulvestrant 500mg and fulvestrant 250mg.
2015-12-16 | GSE76040 | GEO
Project description:Menopausal estrogen (E2) replacement therapy increases the risk of estrogen receptor (ER)-positive epithelial ovarian cancers (EOC). Whether E2 is tumorigenic or promotes expansion of undiagnosed pre-existing disease is unknown. To determine E2 effects on tumor promotion, we developed an intraperitoneal mouse xenograft model using ZsGreen fluorescent ER- 2008 and ER+ PEO4 human EOC cells. Tumor growth was quantified by in vivo fluorescent imaging. In ER+ tumors, E2 significantly increased size, induced progesterone receptors, and promoted lymph node metastasis, confirming that ER are functional and foster aggressiveness. Laser captured human EOC cells from ER- and ER+ xenografted tumors were profiled for expression of E2-regulated genes. Three classes of E-regulated EOC genes were defined, but less than 10% were shared with E-regulated breast cancer genes. Since breast cancer selective ER modulators (SERM) are therapeutically ineffective in EOC, we suggest that our EOC-specific E-regulated genes can assist pharmacologic discovery of ovarian targeted SERM. 15 samples were included in this experiment with a 2x2 factorial design with 2 different cell lines (2008 and PEO4) and 2 different hormone treatments (E for Estrogen and C for Placebo Control) and 4 replicates per treatment. 1 sample was excluded (a replicate of PEO4 with C treatment) because of poor quality.
2011-05-13 | E-GEOD-22600 | biostudies-arrayexpress
Project description:Degradation and chemical modification of RNA in formalin-fixed paraffin-embedded (FFPE) samples hamper their use in expression profiling studies. In this study, we investigated the feasibility of gene expression signature generation from archival FFPE materials. Nineteen cervical squamous cell carcinoma (SCC) and nine adenocarcinoma (AC) 10~16-year-old FFPE samples were profiled using Affymetrix Exon 1.0 ST arrays. A comparison of the global gene expression changes between SCC and AC revealed 1217 differentially expressed genes. Of these, 1062 showed significantly higher expression levels in SCC relative to AC, and 155 genes were found to be specifically upregulated in AC. When the 1217-gene signature was tested on a fresh-frozen human non-small cell lung cancer (NSCLC) series, it correctly separated the 58 NSCLC samples into SCC and AC. In conclusion, our results showed that clinically and biologically relevant gene expression profiles can be derived from FFPE samples with Exon array profiling. The study population contains 28 FFPE human cervix samples (19 SCC and 9 AC). Histopathology assessment and p63 IHC were performed on all samples to confirm their histological subtypes. Total RNA was extracted and hybridised to Affymetrix Human Exon 1.0 ST arrays. Expression values were normalised using RMA. Only exonic probesets that were flagged as present (DABG< 0.01) in at least three samples were retained for further analysis. LIMMA was used to identify probesets that were differentially expressed between SCC and AC subtypes, using FDR ≤ 0.01 and absolute fold-change ≥ 2 as cutoff.
2011-02-17 | E-GEOD-27388 | biostudies-arrayexpress
Project description:Anti neutrophil cytoplasmic antibody (ANCA) associated vasculitis is the most frequent cause of crescentic glomerulonephritis. Histopathologic features and clinical course of the disease are diverse and judgment of disease activity is often limited due to the lack of reliable activity markers. In order to define potentially new molecular or cellular markers in the kidney which may predict clinical outcome, we performed microarray analyses of renal biopsies from patients with ANCA-associated crescentic glomerulonephritis. We correlated expression profiles with clinical data from our prospective study of patients with renal ANCA disease. The CC chemokine ligand 18 (CCL18) was one of the most up-regulated proteins in kidneys of patients with ANCA-associated crescentic glomerulonephritis. CCL18 producing cells in the kidneys were identified as CD68 and CD209 positive myeloid dendritic cells. The density of CCL18 positive cells correlated with the severity of acute tubular injury and with the impairment of renal function. CCL18 protein levels were elevated in serum samples of patients with renal ANCA disease when compared with patients with non- ANCA-associated crescentic glomerulonephritis. Persistence of high CCL18 serum levels correlated with impairment of renal function and the risk of relapsing disease. Therefore, CCL18 might serve as a marker for persistent disease activity and renal relapses in ANCA-associated vasculitis.
2015-09-03 | E-MTAB-1944 | biostudies-arrayexpress
Project description:Invasive lobular cancer (ILC) accounts for approximately 10-15% of breast carcinomas and although it responds poorly to neoadjuvant chemotherapy, it appears to respond well to endocrine therapy. Pre- and on-treatment (after 2 weeks and 3 months) biopsies and surgical samples were obtained from 14 post-menopausal women with ER+ histologically confirmed ILC who responded to 3 months of neoadjuvant letrozole and were compared with a cohort of 14 responding infiltrating ductal carcinomas (IDCs) matched on clinicopathological features by gene expression profiling. Dynamic clinical response was assessed using periodic 3D ultrasound measurements performed during treatment and defined as a reduction of >70% in tumour volume by 3 months. The changes in gene expression in response to letrozole were highly consistent between responding ILC and IDC tumours, genes involved in proliferation were down-regulated and those involved with immune function and ECM remodelling were up-regulated. However, molecular differences between the histological subtypes were maintained upon treatment. This is the first study of molecular changes in ILC in response to endocrine therapy to date. The genes which change on letrozole are highly consistent between ILC and IDC. Differences in gene expression between ILC and IDC at diagnosis and are maintained at each time point on treatment. 14 Pre treatment, 10 two week and 14 three month on-treatment ILC and 14 Pre treatment, 14 two week and 14 three month on-treatment IDC samples from the same patients. Pre- and on-treatment samples from 7ILC & 6IDC patients were profiled on Illumina HT-12v4 (GPL10558) and samples from 7ILC and 8 IDC patients were profiled previously on Affymetrix U133A (GPL96) see GSE20181
2014-08-11 | E-GEOD-55374 | biostudies-arrayexpress
Project description:Immunotherapy provides an alternative approach for cancer treatment. However, in-depth analyses of the effects of immunotherapy on the tumor microenvironment (TME) have not been conducted in non-melanoma tumors. Here we describe changes in the pancreatic ductal adenocarcinoma (PDAC) TME following immunotherapy treatment, and show for the first time that vaccine-based immunotherapy directly alters the TME, inducing neogenesis of tertiary lymphoid structures that convert immunologically quiescent tumors into immunologically active tumors. Alterations in five pathways important for immune modulation and lymphoid structure development (TH17/Treg, NFkB, Ubiquitin-proteasome, Chemokines/chemokine receptors, and Integrins/adhesion molecules) in vaccine-induced intratumoral lymphoid aggregates were associated with improved post-vaccination responses. Additional studies in other cancers and patients treated with other forms of immunotherapy are warranted to further develop signatures defined in intratumoral lymphoid structures into biomarkers that predict effective anti-tumor immune responses. These signatures may also expose therapeutic targets for promoting more robust antitumor immune responses in the TME. Between July 2008 and September 2012, 59 patients were enrolled into an ongoing study of an irradiated, allogeneic GM-CSF-secreting pancreatic tumor vaccine (GVAX) administered intradermally either alone or in combination with immune modulatory doses of cyclophophamide (Cy) as neoadjuvant and adjuvant treatment for patients with resectable pancreatic ductal adenocarcinoma (PDAC). Patients were randomized 1:1:1 to 3 treatment arms. In Arm A, patients received GVAX alone; in Arm B, patients received GVAX plus a single intravenous dose of Cy at 200 mg/m2 1 day prior to each vaccination; in Arm C, patients received GVAX plus oral Cy at 100 mg once daily for 1 week on and 1 week off. Up to 6 GVAX treatments were administered and all of the patients remained in their initial treatment arms throughout the duration of the study. All 59 of the patients received the 1st GVAX treatment 2 weeks +/-4 days prior to surgery. Formalin-fixed paraffin-embedded (FFPE) tissue blocks of surgically resected PDAC were obtained from the pathology archive. FFPE tissue blocks from each subject were stained by H&E immediately before the vaccine therapy-induced lymphoid aggregates were microdissected . To better understand the functional status of these vaccine therapy induced lymphoid aggregate structures, gene microarray analysis on RNA isolated from microdissected lymphoid aggregates was performed. Gene expression was compared among samples grouped according to patient overall survival, post-vaccination induction of enhanced mesothelin-specific T cell responses in peripheral blood lymphocytes (PBL), and the intratumoral CD8+ T effector to FoxP3+ Treg ratio. Post-vaccination induction of enhanced mesothelin-specific T cell responses has been reported to correlate with longer survival in patients treated with Panc GVAX.
2014-08-05 | E-GEOD-52171 | biostudies-arrayexpress
Project description:Current prognostic factors are poor at identifying patients at risk of disease recurrence following surgery for stage II colon cancer. Here we describe a DNA microarray based prognostic assay using clinically relevant formalin fixed paraffin embedded (FFPE) samples.
2011-11-22 | E-MTAB-864 | biostudies-arrayexpress
Project description:Purpose Aromatase inhibitors (AIs) have an established role in breast cancer treatment. Response rates are only 50-70% in the neoadjuvant setting and lower in advanced disease. Accurate biomarkers are urgently needed to predict response in these settings and to determine which individuals will benefit from adjuvant AI therapy. Participants and Methods Pre- and on-treatment (after 2 weeks and 3 months) biopsies were obtained from 89 post-menopausal women with ER+ breast cancer receiving neoadjuvant letrozole for transcript profiling. Dynamic clinical response was assessed by three-dimensional ultrasound measurements. Results The molecular response to letrozole was characterised and a four gene classifier of clinical response was established (accuracy of 96%) based upon the level of two genes prior to treatment (one associated with immune signalling, IL6ST and the other with apoptosis, NGFRAP1) and two proliferation genes (ASPM, MCM4) at 2 weeks of therapy. The four gene signature was found to be 91% accurate in a blinded, completely independent validation dataset of patients treated with anastrozole. Matched 2 week on-treatment biopsies improved predictive power over pre-treatment biopsies alone. This signature also significantly predicted recurrence free survival (p=0.029) and breast cancer specific survival (p=0.009). We demonstrate that the test can also be performed using quantitative PCR or immunohistochemistry. Conclusion A four gene predictive model of clinical response to AIs by two weeks has been generated and validated. Deregulated immune and apoptotic responses before treatment and a failure to reduce proliferation by 2 weeks are functional characteristics of breast tumours that do not respond to AIs. 25 Pre treatment, 25 two week and 25 three month on-treatment primary breast tumour samples from the same patients. Data was analysed with two previously generated datasets, GSE55374 which was also processed on Illumina HT-12v4 BeadChips (GPL10558) and GSE20181 on Affymetrix U133A GeneChips (GPL96)
2015-07-06 | E-GEOD-59515 | biostudies-arrayexpress
Project description:Current prognostic factors are poor at identifying patients at risk of disease recurrence following surgery for stage II colon cancer. Here we describe a DNA microarray based prognostic assay using clinically relevant formalin fixed paraffin embedded (FFPE) samples.
2011-11-22 | E-MTAB-863 | biostudies-arrayexpress
Project description:The NEWEST (Neoadjuvant Endocrine Therapy for Women with Estrogen-Sensitive Tumours) trial compared the clinical and biological activity of fulvestrant 500 mg vs 250 mg in the neoadjuvant setting. In this multi-centre phase II study, post-menopausal women with operable, locally advanced (T2, 3, 4b; N0-3; M0) ER-positive breast tumours were randomised to receive neoadjuvant treatment with either dose of fulvestrant for 16 weeks before surgery. Tumour core biopsies were obtained at baseline, 4 weeks and at surgery for assessment of changes in biomarker expression. Tumour volumes were measured by 3-D ultrasound at the same timepoints. In this trial, the percentage of patients who showed a reduction in tumour volume or stabilisation of disease (using RECIST criteria) after treatment with fulvestrant 500 mg was 36% (26 out of 69 patients). Therefore, within a population of endocrine-therapy naive patients whose tumours were confirmed as being ER-positive at the time of study entry, there is a subgroup who gained particular clinical benefit from fulvestrant treatment. These clinical response data together with the availability of biological response information and frozen tumour tissue from participants makes the NEWEST trial an attractive setting in which to investigate the potential of new markers of response to fulvestrant. 42 samples
2014-01-08 | E-GEOD-48905 | biostudies-arrayexpress