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.
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
Project description:In this study, we report a broad analysis of central tumor samples (C), from both Glioblastoma long term survivors (LT) and short term ones (ST), integrated by the same analysis performed on peritumoral areas (P) from the same patients. We provide data from SAGE analysis performed with deep sequencing.
Project description:Purpose: Autologous tumor lysate-pulsed dendritic cell (DC) vaccination has shown promising long-term survival in a cohort of patients with newly diagnosed glioblastoma. The purpose of this study was to better understand the mechanisms and modulation of the immune microenvironment underlying the clinical efficacy of DC-based vaccine therapy. Experimental Design: We performed bulk RNA sequencing on tumor samples from patients with newly diagnosed glioblastoma obtained prior to treatment with dendritic cell vaccination. We characterized the molecular mechanisms and immune microenvironments of long-term survivors (LTS, n= 8), medium-term survivors (MTS, n= 13), and short-term survivors (STS, n = 17). Results: There was an enrichment of the mesenchymal subtype of glioblastoma in the long-term survival group. Additionally, decreased tumor cell density, upregulation of cell surface markers, and increased neuronal activity were associated with the longer survival cohorts. Two microglia populations, one associated with increased survival and one associated with decreased survival in the DC-treated cohorts, but not standard of care (SOC) cohorts, are also potentially implicated in response to DC immunotherapy. There were increases in functional activity of the immune environment in longer survivor cohorts. Conclusions: These analyses suggest the potential to identify tumor-based predictive factors that may be associated with favorable responses to DC vaccination in glioblastoma patients; and if validated, these findings may enable better patient selection for future clinical trials.
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
