Expression data from primary Glioblastoma in adults
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE53733 | GEO | 2014/03/27
SECONDARY ACCESSION(S): PRJNA232732
REPOSITORIES: GEO
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Project description:Gene expression profiling revealed over-representation of a distinct (proneural-like) expression signature in long-term survivors that was linked to IDH1/2 mutation. However, among the IDH1/2-wildtype patients, tumors from long-term survivors did not show distinct gene expression profiles and included proneural, classical and mesenchymal glioblastoma subtypes. We performed genome- and/or transcriptome-wide molecular profiling of primary tumor samples from 70 glioblastoma patients of the German Glioma Network, including 23 longterm survivors with >36 months overall survival (OS), 16 short-term survivors with <12 months OS, and 31 patients with intermediate OS For this study, we screened prospectively recruited patients with a histopathological reference diagnosis of glioblastoma, known KPS at diagnosis, information on extent of resection by early postoperative neuroimaging, available frozen tissue specimens from the initial operation, and documented clinical outcome.
2014-03-27 | E-GEOD-53733 | biostudies-arrayexpress
Project description:The AVAglio and RTOG-0825 randomized, placebo-controlled phase III trials in newly diagnosed glioblastoma reported prolonged progression-free survival (PFS), but not overall survival (OS), with the addition of bevacizumab to radiotherapy/temozolomide. To establish whether certain patient subgroups derived OS benefit from the addition of bevacizumab to first-line standard-of-care therapy, AVAglio patients were retrospectively evaluated for molecular subtype, and bevacizumab efficacy assessed for each patient subgroup. A multivariate analysis accounting for prognostic covariates revealed that bevacizumab conferred a significant OS advantage versus placebo for patients with Proneural IDH1 wild-type tumors (17.1 v 12.8 months, respectively; hazard ratio, 0.43; 95% CI, 0.26 to 0.73; P = .002). This analysis also revealed an interaction between the Proneural subtype biomarker and treatment arm (P = .023). The group of patients with Mesenchymal and Proneural tumors derived a PFS benefit from bevacizumab, compared with placebo; however, this translated to an OS benefit in the Proneural subset only. Retrospective analysis of AVAglio data suggests that patients with IDH1 wild-type Proneural glioblastoma may derive OS benefit from first-line bevacizumab treatment. The predictive value of the Proneural subtype observed in AVAglio should be validated in an independent dataset. A total of 349 (bevacizumab arm, n = 171; placebo arm, n = 178) pretreatment specimens from AVAglio patients (total n = 921) were available for biomarker analysis. Samples were profiled for gene expression and isocitrate dehydrogenase 1 (IDH1) mutation status and classified into previously identified molecular subtypes. PFS and OS were assessed within each subtype.
2016-07-06 | E-GEOD-84010 | biostudies-arrayexpress
Project description:The AVAglio and RTOG-0825 randomized, placebo-controlled phase III trials in newly diagnosed glioblastoma reported prolonged progression-free survival (PFS), but not overall survival (OS), with the addition of bevacizumab to radiotherapy/temozolomide. To establish whether certain patient subgroups derived OS benefit from the addition of bevacizumab to first-line standard-of-care therapy, AVAglio patients were retrospectively evaluated for molecular subtype, and bevacizumab efficacy assessed for each patient subgroup. A multivariate analysis accounting for prognostic covariates revealed that bevacizumab conferred a significant OS advantage versus placebo for patients with Proneural IDH1 wild-type tumors (17.1 v 12.8 months, respectively; hazard ratio, 0.43; 95% CI, 0.26 to 0.73; P = .002). This analysis also revealed an interaction between the Proneural subtype biomarker and treatment arm (P = .023). The group of patients with Mesenchymal and Proneural tumors derived a PFS benefit from bevacizumab, compared with placebo; however, this translated to an OS benefit in the Proneural subset only. Retrospective analysis of AVAglio data suggests that patients with IDH1 wild-type Proneural glioblastoma may derive OS benefit from first-line bevacizumab treatment. The predictive value of the Proneural subtype observed in AVAglio should be validated in an independent dataset.
2016-07-06 | GSE84010 | GEO
Project description:Glioblastoma (GBM) is a highly aggressive type of glioma with poor prognosis. However, a small number of patients live much longer than the median survival. A better understanding of these long-term survivors (LTS) may provide important insight into the biology of GBM. We identified 7 patients with GBM treated at Memorial Sloan-Kettering Cancer Center (MSKCC) with survival greater than 48 months. We characterized the transcriptome of each patient and determined rates of MGMT promoter methylation and IDH1 and IDH2 mutational status. We identified LTS in two independent cohorts (TCGA and REMBRANDT) and analyzed the transcriptomal characteristics of these LTS. The median overall survival of our cohort was 62.5 months. LTS were distributed between the proneural (n=2), neural (n=2), classical (n=2) and mesenchymal (n=1) subtypes. Similarly, LTS in the TCGA and REMBRANDT cohorts demonstrated diverse transcriptomal subclassification identity. The majority of the MSKCC LTS (71%) were found to have methylation of the MGMT promoter. None of the patients had an IDH1 or IDH2 mutations, and IDH mutation occurred in a minority of the TCGA LTS as well. A set of 42 genes was found to be differentially expressed in the MSKCC and TCGA LTS. While IDH mutant proneural tumors impart a better prognosis in the short-term, survival beyond 4 years does not require IDH mutation and is not dictated by a single transcriptional subclass. In contrast, MGMT methylation continues to have strong prognostic value for survival beyond 4 years. These findings have substantial impact for understanding GBM biology and progression.
2014-05-02 | GSE54077 | GEO
Project description:Glioblastoma is a devastating CNS tumor for which median survival remains only 14-18 months. Homologous antigenic loading provides a powerful PAMP signal that initiates cDC1-like skewing of monocyte-derived DC and downstream development of tissue-homing, cytolytic memory effectors. Here we report results of a phase I trial in which DC vaccines prepared through homologous antigenic loading were administered principally to newly-diagnosed MGMT unmethylated GBM patients. AEs were mild, with none >grade 2 attributable to the regimen. Enrolled patients exhibited post-vaccination elevations in central memory and MPEC cells in peripheral blood, evidence of in situ immune responses by spatial transcriptomics, and a vaccine cell gene signature that correlated with outcomes. One-year OS of the 15/16 MGMT unmethylated newly-diagnosed cohort was 87.5%. Among nine patients who did not receive reoperation, GBM-specific OS was 88.9% with median OS yet-to-be-reached after 17.2 months follow-up among this group and late pseudoprogression notable among long-term survivors.
2024-12-06 | GSE283576 | GEO
Project description:Glioblastoma (GBM) is a highly aggressive type of glioma with poor prognosis. However, a small number of patients live much longer than the median survival. A better understanding of these long-term survivors (LTS) may provide important insight into the biology of GBM. We identified 7 patients with GBM treated at Memorial Sloan-Kettering Cancer Center (MSKCC) with survival greater than 48 months. We characterized the transcriptome of each patient and determined rates of MGMT promoter methylation and IDH1 and IDH2 mutational status. We identified LTS in two independent cohorts (TCGA and REMBRANDT) and analyzed the transcriptomal characteristics of these LTS. The median overall survival of our cohort was 62.5 months. LTS were distributed between the proneural (n=2), neural (n=2), classical (n=2) and mesenchymal (n=1) subtypes. Similarly, LTS in the TCGA and REMBRANDT cohorts demonstrated diverse transcriptomal subclassification identity. The majority of the MSKCC LTS (71%) were found to have methylation of the MGMT promoter. None of the patients had an IDH1 or IDH2 mutations, and IDH mutation occurred in a minority of the TCGA LTS as well. A set of 42 genes was found to be differentially expressed in the MSKCC and TCGA LTS. While IDH mutant proneural tumors impart a better prognosis in the short-term, survival beyond 4 years does not require IDH mutation and is not dictated by a single transcriptional subclass. In contrast, MGMT methylation continues to have strong prognostic value for survival beyond 4 years. These findings have substantial impact for understanding GBM biology and progression. All tumors (n = 7) were obtained following surgical resection at the MSKCC as part of routine clinical care, and snap frozen. Tumors were obtained in accordance with Institutional Review Board policies at the MSKCC. Each sample was examined histologically by 3 independent neuropathologists and confirmed to be World Health Organization (WHO) grade IV glioma (GBM). Before analysis, tumors were sectioned and microdissected. Genomic DNA or RNA was extracted using the DNeasy kit (Qiagen) or RNeasy Lipid Tissue Mini Kit (Qiagen) as per the manufacturer’s instructions. Expression analysis of tumors was performed using the Affymetrics U133 2.0 microarray (Affymetrix). Affymetrix CEL files were imported into the Partek Genomics Suite (Partek). The TCGA gene expression data (HT-HG-U133A) was accessed from the TCGA data repositories (http://cancergenome.nih.gov, date of download 12/2013).
2014-05-02 | E-GEOD-54077 | biostudies-arrayexpress
Project description:Background and aim: Only 10% of pancreatic ductal adenocarcinoma (PDAC) patients survive longer than five years. Factors underlining long-term survivorship in PDAC are not well understood. Therefore, we aimed to identify the key players in the tumor immune microenvironment (TIME) associated with long-term survivorship in PDAC patients. Methods: The immune-related gene expression profiles of resected PDAC tumors of patients who survived and remained recurrence-free of disease for ≥36 months (long-term survivors, n=10) were compared to patients who had survived ≤6 months (short-term survivors, n=10) due to tumor recurrence. Validation was performed by the spatial protein expression profile of immune cells using the GeoMx™ Digital Spatial Profiler. An independent cohort of samples consisting of 12 long-term survivors and 10 short-term survivors, was used for additional validation. The independent validation was performed by combining qualitative immunohistochemistry and quantitative proteinexpression profiling. Results: B cells were found to be significantly increased in the TIME of longterm survivors by gene expression profiling (p=0.018). The high tumor infiltration of B cells was confirmed by spatial protein profiling in the discovery and the validation cohorts (p=0.002 and p=0.01, respectively). The higher number of infiltrated B cells was found mainly in the stromal compartments of PDAC samples and was exclusively found within tumor cells in long-term survivors. Conclusion: This is the first comprehensive study that connects the immune landscape of gene expression profiles and protein spatial infiltration with the survivorship of PDAC patients. We found a higher number and a specific location of B cells in TIME of long-term survivors which emphasizes the importance of B cells and B cell-based therapy for future personalized immunotherapy in PDAC patients.
2022-12-14 | GSE220929 | GEO
Project description:Glioblastoma multiforme (GBM) is the most common and deadliest primary brain tumor. Its prognosis is inexorably unfavorable, as these tumors drive affected patients to death usually within 15 months after diagnosis (short term survivors, ST), with the only exception of a small fraction of patients (long term survivors, LT) surviving longer than 36 months. Even after the frontline therapeutic approach, including surgical resection followed by chemo- and radiotherapy, the cause of death in most cases is tumor recurrence, which occurs in peritumoral tissues in about 95% of patients. Here, we provide a comprehensive molecular analysis of a set of ST and LT samples derived from frankly tumoral areas (C) and from the peritumoral regions (P) of the same patients. By performing microRNA deep sequencing, we collected data showing that P areas differ from healthy white matter, but share with C samples, a number of microRNAs
2017-03-08 | E-MTAB-3239 | biostudies-arrayexpress
Project description:Osteosarcoma (OS) accounts for approximately 80% of all malignant bone tumors in the dog. Tumors are highly metastatic and long-term survival is poor. This study aims to investigate the prognosis associated gene expression profile in primary canine OS. Canine specific cDNA microarray representing 20,313 genes was used to analyze expression profiles in a panel of thirty-two primary osteosarcoma to identify genes associated with survival. The 32 tumours were classified into two groups of prognosis based on survival time (ST). They were defined as short survivors (dogs with poor prognosis that survived less than 6 months) and long survivors (dogs with better prognosis that survived longer than 6 months). Fifty-one genes were found to be differentially expressed, with common up regulation of these genes in the short survivors. The overexpression of these genes in short survivors suggests a possible role for increased proliferation, drug resistance or metastasis. Several deregulated pathways were identified in the present study includes Wnt signaling, Integrin signaling and Chemokine / cytokine signaling which were comparable to the pathway analysis conducted on human OS, adding more value for the dog as an excellent model to study human OS. Our results suggest that a molecular-based method for discrimination of outcome for short survivors and long survivors of canine OS may be useful for future prognostic stratification of dogs at initial diagnosis, where genes and pathways associated with cell cycle/ proliferation, drug resistance and metastasis could be potential targets for therapy that may not just be beneficial for dogs but also for humans.
2009-09-14 | GSE14033 | GEO
Project description:Purpose/Objective(s): To correlate gene expression and overall survival (OS) in patients with pancreatic adenocarcinoma who have undergone definitive surgery Materials/Methods: Patients were identified that were treated with definitive surgery without neoadjuvant and adjuvant therapy for pancreatic adenocarcinoma. The Beaumont BioBank consented patients then collected and stored tissue samples. Patients were grouped into short term (<10 months, n=13) and long term (>20 months, n=11) survivors. RNA was extracted from fresh frozen tissues, and global gene expression patterns in the short and longer-term survivors were compared. Pathway analysis of the significant genes was also performed. Results: The median age at the time of surgery was 64 years. The mean overall survival in each group was 7.5 months and 32.0 months. We identified 163 genes that were differentially expressed between patients who survived <10 months and >20 months from their definitive surgery. Many of the genes identified have known prognostic importance in oncology; however, less than half of these genes have been reported to be associated with survival in pancreatic adenocarcinoma. Pathway analysis identified expression targets of SP1, JUN, and EGF to be highly regulated based upon differences in overall survival. Conclusions: In pancreatic adenocarcinoma patients who have undergone definitive resection, we have identified multiple genes associated with inferior survival. Many of the genes reported in this study have not previously been linked to overall survival in this patient population.
2017-12-01 | GSE77435 | GEO