Impact of Genomic and Clinical Factors on Outcome of Children ≥18 Months of Age with INSS Stage 3 Neuroblastoma with Unfavorable Histology without MYCN Amplification
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE218527 | GEO | 2023/01/26
REPOSITORIES: GEO
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Project description:The stabilization of MYCN by FOXR2 represents an alternative mechanism to MYCN amplification to increase MYCN protein levels. As such, FOXR2 expression identifies another subset of neuroblastoma patients with unfavorable clinical outcome. Background: Clinical outcomes of neuroblastoma patients range from spontaneous tumor regression to fatality. Hence, understanding the mechanisms that cause tumor progression are crucial for the treatment of patients. In this study, we show that FOXR2 activation identifies a subset of neuroblastoma tumors with unfavorable outcome and we investigate the mechanism how FOXR2 relates to poor outcome in patients.
2021-10-13 | GSE156092 | GEO
Project description:Background: Early prognostication is a major challenge after out-of-hospital cardiac arrest (OHCA). Aims: We hypothesized that a genome-wide analysis of blood gene expression could offer new prognostic tools and lines of research. Methods: Sixty-nine patients were enrolled from an ancillary study of the clinical trial NCT00999583 that tested the effect of erythropoietin (EPO) after OHCA. Blood samples were collected in comatose survivors of OHCA at hospital admission and 1 and 3 days after resuscitation. Gene expression profiles were analyzed (Illumina HumanHT-12 V4 BeadChip; >34,000 genes). Patients were classified into two categories representing neurologically favorable outcome (Cerebral Performance Category [CPC] = 1-2) vs unfavorable outcome (CPC>2) at Day 60 after OHCA. Differential and functional enrichment analyses were performed to compare transcriptomic profiles between these two categories. Results: Among the 69 enrolled patients, 33 and 36 patients were treated or not by EPO, respectively. Among them, 42% had a favorable neurological outcome in both groups. EPO did not affect the transcriptomic response at Day-0 and 1 after OHCA. In contrast, 76 transcripts differed at Day-0 between patients with unfavorable vs favorable neurological outcome. This signature persisted at Day-1 after OHCA. Functional enrichment analysis revealed a down-regulation of adaptive immunity with concomitant up-regulation of innate immunity and inflammation in patients with unfavorable vs favorable neurological outcome. The transcription of many genes of the HLA family was decreased in patients with unfavorable vs favorable neurological outcome. Concomitantly, neutrophil activation and inflammation were observed. Up-stream regulators analysis showed the implication of numerous factors involved in cell cycle and damages. A logistic regression including a set of genes allowed a reliable prediction of the clinical outcomes (Specificity=88%; Hit Rate=83%). Conclusions: A transcriptomic signature involving a counterbalance between adaptive and innate immune responses is able to predict neurological outcome very early after hospital admission after OHCA. This deserves confirmation in a larger population.
2019-03-21 | E-MTAB-7699 | biostudies-arrayexpress
Project description:This data set was used to study FLT3 wild type and mutants in childhood AML samples from the Pediatric Oncology Group Study 9421. Abstract: Fms-like tyrosine kinase 3 (FLT3) mutations are associated with unfavorable outcomes in children with acute myeloid leukemia (AML). We used DNA microarrays to identify gene expression profiles related to FLT3 status and outcome in childhood AML. Among 81 diagnostic specimens, 36 had FLT3 mutations (FLT3-MUs), 24 with internal tandem duplications (ITDs) and 12 with activating loop mutations (ALMs). In addition, 8 of 19 specimens from patients with relapses had FLT3-MUs. Predictive analysis of microarrays (PAM) identified genes that differentiated FLT3-ITD from FLT3-ALM and FLT3 wild-type (FLT3-WT) cases. Among the 42 specimens with FLT3-MUs, PAM identified 128 genes that correlated with clinical outcome. Event-free survival (EFS) in FLT3-MU patients with a favorable signature was 45% versus 5% for those with an unfavorable signature (P = .018). Among FLT3-MU specimens, high expression of the RUNX3 gene and low expression of the ATRX gene were associated with inferior outcome. The ratio of RUNX3 to ATRX expression was used to classify FLT3-MU cases into 3 EFS groups: 70%, 37%, and 0% for low, intermediate, and high ratios, respectively (P < .0001). Thus, gene expression profiling identified AML patients with divergent prognoses within the FLT3-MU group, and the RUNX3 to ATRX expression ratio should be a useful prognostic indicator in these patients. A clinical history design type is where the organisms clinical history of diagnosis, treatments, e.g. vaccinations, surgery etc. Computed
2006-01-06 | E-GEOD-3986 | biostudies-arrayexpress
Project description:We used gene expression profiling and pathway impact analyses to search signaling pathways, which mediate crosstalk between lymphoma cells and tumor-infiltrating inflammatory cells and contribute to the outcome of follicular lymphoma (FL) patients. 24 FL patients treated with rituximab and CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy were classified into groups of favorable or adverse outcomes, and the transcripts differentially expressed in the pretreatment FL tissues between the groups were analyzed.
2009-08-15 | E-MEXP-2305 | biostudies-arrayexpress
Project description:Despite recent consensus on eligibility of adjuvant systemic therapy in lymph-node negative breast cancer (NNBC) patients based on clinico-pathological criteria, specific biological markers are needed to predict sensitivity to the different therapeutic options. We examined the feasibility of developing a genomic predictor of chemotherapy response and recurrence risk in 185 patients with NNBC using assembled arrays containing 2,460 BAC clones for scanning the genome for DNA copy number changes. After surgery, 90 patients received anthracycline-based chemotherapy whereas ninety-five did not. Tamoxifen was administered to patients with hormone-receptor positive tumors. Association of genomic and clinico-pathological data and outcome was computed using Cox proportional hazard models and multiple testing adjustment procedures. Analysis of NNBC genomes revealed a common genomic signature. Specific DNA copy number aberrations were associated with hormonal receptor status, but not with other clinico-pathological parameters. In patients treated with chemotherapy, none of the genomic changes was significantly correlated with recurrence. In patients not receiving chemotherapy, deletion of eight BAC clones clustered to chromosome 11q was independently associated with relapse (DFS at 10 years±SE, 40±14% vs. 86±6%;p<00001). The 54 patients with deletion of 11q (29%) did not present more aggressive clinical-pathological features than those without 11q loss. The adverse influence of 11q deletion in clinical outcome was confirmed in an independent validation series of 88 NNBC patients. Our data suggest that NNBC patients with 11q deletion may benefit from anthracycline-based chemotherapy despite other clinical, pathological or genetic features. However, these initial findings should be evaluated in randomized clinical trials. Keywords: CGH, breast cancer
2007-02-07 | GSE6448 | GEO
Project description:Twenty-seven CC patients with stage III to IV were recruited in this a single-center, phase I study. TILs were isolated from local or metastatic CC lesions and generated under GMP conditions. Thirteen patients accepted TIL-based ACT and intramuscular IL-2 following CCRT or CT treatment. Outcomes were classified as patients with a poor outcome (nonresponders) and patients with a favorable outcome (responders). Single cell RNA sequencing (scRNA-seq) for infused TIL products in responder and non-responder.
2022-07-19 | GSE190075 | GEO
Project description:The prognosis of children with metastatic stage 4 neuroblastoma (NB) has remained poor in the past decade. Using microarray analyses of 342 primary tumors, we here developed and validated an easy to use gene expression-based risk score including 18 genes, which can robustly predict the outcome of stage 4 patients. This classifier was a significant predictor of overall survival in two independent validation cohorts (cohort 1 (n=214): P=6.3x10-5; cohort 2 (n=27): P=3.1x10-2). The prognostic value of the risk score was validated by multivariate analysis including the established markers age and MYCN status (P=0.027). In the pooled validation cohorts (n=241), integration of the risk score with the age and/or MYCN status identified subgroups with significantly differing overall survival (ranging from 35% to 100%). Together, the 18-gene risk score classifier can identify patients with stage 4 NB with favorable outcome and may therefore improve risk assessment and treatment stratification of NB patients with disseminated disease. We analyzed expression profiling arrays of 27 Tumor samples from stage 4 neuroblastoma patients.
2016-04-05 | E-GEOD-79910 | biostudies-arrayexpress
Project description:PURPOSE: To evaluate frequency, biological features and clinical relevance of RUNX1 mutations in acute myeloid leukemia (AML). PATIENTS AND METHODS: Diagnostic samples from 945 patients (18 to 60 years) were analyzed for RUNX1 mutations. In a subset of cases (n=269) microarray gene expression analysis was performed. RESULTS: Fifty-nine RUNX1 mutations were identified in 53 of 945 (5.6%) cases, predominantly in exons 3 (n=11), 4 (n=10) and 8 (n=23). RUNX1 mutations clustered in the intermediate-risk cytogenetic group (46/640, 7.2%; cytogenetically normal, 34/538, 6.3%), they were less frequent in adverse-risk cytogenetics (5/109, 4.6%), and absent in core-binding-factor AML (0/77) and acute promyelocytic leukemia (0/61); RUNX1 mutations were associated with MLL-partial tandem duplications (p=0.0007) and IDH1/IDH2 mutations (p=0.03), inversely correlated with NPM1 (p<0.0001) and in trend with CEBPA (p=0.10) mutations. RUNX1 mutations were characterized by a distinct gene expression pattern; this RUNX1 mutation-derived signature was not exclusive for the mutation, but also included mostly adverse-risk AML [eg, 7q-, -7, inv(3) or t(3;3)]. RUNX1 mutations predicted for resistance to chemotherapy (rates of refractory disease 30% and 19%, p=0.047, for RUNX1-mutated and wildtype patients, respectively), as well as inferior event-free survival (EFS; p<0.0001), relapse-free survival (RFS, p=0.022), and overall survival (p=0.051). In multivariable analysis, RUNX1 mutations were an independent prognostic marker for shorter EFS (p=0.007). Explorative subgroup analysis revealed that allogeneic hematopoietic stem cell transplantation had a favorable impact on RFS in RUNX1-mutated patients (p<0.0001). CONCLUSION: AML with RUNX1 mutations exhibit distinct biological properties and are associated with resistance to therapy and inferior outcome. A total of 269 RNA samples derived from adult AML patients were provided by the German Austrian AML Study Group (AMLSG) [AMLSG trial AML HD98A (ClinicalTrials.gov Identifier: NCT00146120)]. Conventional cytogenetic banding, and FLT3, CEBPA and NPM1 mutational analysis were performed as previously described (Schlenk et al., N Engl J Med 2008). Detailed clinical, cytogenetic and molecular cytogenetic information are also provided in the supplementary information. Following enrichment, all samples contained at least 80% leukemic cells. Gene expression profiling (GEP) was performed as previously described (Bullinger et al., N Engl J Med 2004).
2010-12-31 | E-GEOD-23312 | biostudies-arrayexpress
Project description:In neuroblastoma (NB), the presence of segmental chromosome alterations (SCA) is associated with a higher risk of relapse, even when occurring together with numerical chromosome alterations (NCA). Furthermore, recent evidence shows that SCAs play a role in tumor progression. In order to analyze the role of SCAs in infants with NB, we have performed an extensive retrospective array-CGH analysis of tumours from infants enrolled in the European INES 99.1, 99.2 and 99.3 trials. Tumour samples from 221/300 enrolled patients could be analyzed. SCAs were observed in 11%, 20% and 59% of infants enrolled in trial 99.1 (localised unresectable NB), 99.2 (INSS stage 4s) and 99.3 (INSS stage 4), respectively (p<0.001), and were associated with the presence of bone metastasis (p<0.003). Progression-free survival was poorer in patients whose tumours harbored at least one SCA, in the whole population as well as in trials 99.1 and 99.2. In multivariate analysis, taking into account single genetic alterations, the protocol arm and genomic profile, the SCA genomic profile was the strongest predictor of poor outcome. Although overall survival was excellent, patients with stage 4s disease and a SCA genomic profile had a higher risk of relapse also in the absence of clinical symptoms at diagnosis and required a higher treatment burden for salvage. In conclusion, in infants with NB, a SCA genomic profile is useful to identify patients who will require upfront treatment even in the absence of other clinical indication for therapy, whereas an NCA genomic profile can identify a patient subpopulation in whom treatment reduction can be considered safe. Each of the 218 tumoral genomic DNAs was hybridized against non-tumoral DNA reference on BAC/PAC array or commercial supports in order to determine an overall genomic profile. The reference DNA was obtained from the blood of a single normal individual.
2011-12-07 | E-GEOD-26494 | biostudies-arrayexpress
Project description:Genomic profiles and prognostic biomarkers in patients with acute myeloid leukemia (AML) from ancestry diverse populations are underexplored. We analyzed the exomes and transcriptomes of 100 Black patients with AML (Alliance) and compared somatic mutation frequencies with those of 323 White patients (BeatAML). Seventy-three percent of 162 recurrent gene mutations identified in Black patients, including a novel PHIP alteration detected in 7% of patients, were found in only ≤1 White patient. Black patients with myelodysplasia-related AML were younger than White patients suggesting intrinsic and/or extrinsic dysplasia-causing stressors. On multivariable outcome analyses of Black patients, NPM1 and NRAS mutations associated with inferior disease-free and IDH1/2 mutations with reduced overall survival. Inflammatory profiles, cell type distributions and transcriptional profiles differed between Black and White NPM1-mutated patients. Incorporation of ancestry-specific risk markers into the 2022 European LeukemiaNet genetic-risk stratification changed risk-group assignment for one-third of Black patients and improved their outcome prediction.
2024-05-01 | GSE266099 | GEO