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| Status |
Public on Mar 01, 2018 |
| Title |
A multi-component view of the glioma transcriptome identifies unique immune infiltration patterns in primary glioblastomas and patients with inferior prognosis. |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Patients diagnosed with glioblastomas continue to have a dismal prognosis, highlighting the need for a better characterization of these tumors in order to identify more efficient therapies. In this study, we generated genome-wide expression data from normal brain and glioma samples, representing major glioma subtypes, using exon-level microarrays (n=70). A multi-component approach was used to characterize molecular pathways and tumor infiltrate, with particular focus on the poor prognosis primary glioblastomas (pGBM). Two independent, publically available datasets were used for validation of survival data. Grade II glioma and secondary GBM were enriched in cytotoxic lymphocytes, while pGBM exhibited a heterogeneous cell-related immune infiltrate with high infiltration of monocytic cells. Infiltration by cells of monocytic origin predicted poorer prognosis, regardless of the tumor subtype. High TSPYL2 expression was found to be associated with a poor prognosis in pGBM and to correlate with genes involved in tumor invasion. The multi-component transcriptome phenotypes of pGBM introduced in this study add insights into the main pathways associated with aggressiveness, and identified infiltration by cells of monocytic origin as a universal prognostic marker for all glioma subtypes.
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| Overall design |
The study included 67 glioma samples which were grouped according to the 2016 revision of the WHO classification of tumors of the central nervous system. The study comprised 36 pGBM, 5 sGBM, 18 AII, and 8 OII from glioma patients who underwent surgery at the Department of Neurosurgery (Oslo University Hospital) between June 2006 and April 2010. Patients were included following written informed consent. Permission to include deceased patients was obtained from The National Health Authorities. The study was approved by the Regional Ethics Committee (S-06046) as well as the Institutional Study Board. Histological diagnoses were reviewed by an expert neuropathologist. Four commercially available normal brain total RNA samples were also included (BioChain, B209031, pool of 5 male donors; B306103, one male donor; Clonetech Laboratories, 1004311A, one male donor; Ambion, First Choice Human Brain - 105P055201A, pool of 23 donors). Tumor tissue samples were collected on RNAlater (Qiagen) and total RNA was extracted using a standard TRIzol protocol. Quantity and quality of RNA was assessed by NanoDrop ND-1000 Spectrophotometer (Thermo Fisher Scientific) and Agilent BioAnalyzer 2100 (Agilent Technologies), respectively. All samples were analyzed for global gene expression using Affymetrix Human Exon 1.0. ST Array (Thermo Fisher Scientific). Total RNA (250 ng) was used as input and processed according to the manufacturer's instructions, using the Ambion WT Expression Kit protocol (Ambion), Affymetrix GeneChip WT terminal labeling, and Hybridization User Manual (Affymetrix). Pre-processing and statistical analyses were performed using R version 3.2.2. For each sample, a CEL file storing intensity measures was generated by the Affymetrix GeneChip Command Console software (V.1.0). These files were further processed by background correction, quantile normalization, and summarization at the gene level by the robust multi-array average (RMA) approach using package oligo (version 1.34.2).
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| Contributor(s) |
Jeanmougin M, Håvik AB, Cekaite L, Brandal P, Sveen A, Meling TR, Ågesen TH, Scheie D, Hein S, Lothe RA, Lind GE |
| Citation(s) |
32171051 |
| Submission date |
Feb 28, 2018 |
| Last update date |
May 08, 2020 |
| Contact name |
Jeanmougin Jeanmougin |
| E-mail(s) |
marine.jeanmougin@rr-research.no
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| Organization name |
Norwegian Radium Hospital
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| Department |
Molecular Oncology
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| Lab |
Lind Lab - Epigenetics
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| Street address |
Ullernchausséen 70
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| City |
Oslo |
| ZIP/Postal code |
0379 |
| Country |
Norway |
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| Platforms (1) |
| GPL5175 |
[HuEx-1_0-st] Affymetrix Human Exon 1.0 ST Array [transcript (gene) version] |
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| Samples (70)
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| Relations |
| BioProject |
PRJNA436366 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE111260_RAW.tar |
1.6 Gb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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