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Improved prognostication of glioblastoma beyond molecular subtyping by transcriptional profiling of the tumor microenvironment

Glioblastoma (GBM), the most aggressive form of brain cancer, is characterized by a high level of molecular heterogeneity, and infiltration by various immune and stromal cell populations. Important advances have been made in deciphering the microenvironment of GBMs, but its association with existing...

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Autores principales: Jeanmougin, Marine, Håvik, Annette B., Cekaite, Lina, Brandal, Petter, Sveen, Anita, Meling, Torstein R., Ågesen, Trude H., Scheie, David, Heim, Sverre, Lothe, Ragnhild A., Lind, Guro E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191188/
https://www.ncbi.nlm.nih.gov/pubmed/32171051
http://dx.doi.org/10.1002/1878-0261.12668
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author Jeanmougin, Marine
Håvik, Annette B.
Cekaite, Lina
Brandal, Petter
Sveen, Anita
Meling, Torstein R.
Ågesen, Trude H.
Scheie, David
Heim, Sverre
Lothe, Ragnhild A.
Lind, Guro E.
author_facet Jeanmougin, Marine
Håvik, Annette B.
Cekaite, Lina
Brandal, Petter
Sveen, Anita
Meling, Torstein R.
Ågesen, Trude H.
Scheie, David
Heim, Sverre
Lothe, Ragnhild A.
Lind, Guro E.
author_sort Jeanmougin, Marine
collection PubMed
description Glioblastoma (GBM), the most aggressive form of brain cancer, is characterized by a high level of molecular heterogeneity, and infiltration by various immune and stromal cell populations. Important advances have been made in deciphering the microenvironment of GBMs, but its association with existing molecular subtypes and its potential prognostic role remain elusive. We have investigated the abundance of infiltrating immune and stromal cells in silico, from gene expression profiles. Two cohorts, including in‐house normal brain and glioma samples (n = 70) and a large sample set from TCGA (n = 393), were combined into a single exploratory dataset. A third independent cohort (n = 124) was used for validation. Tumors were clustered based on their microenvironment infiltration profiles, and associations with known GBM molecular subtypes and patient outcome were tested a posteriori in a multivariable setting. We identified a subset of GBM samples with significantly higher abundances of most immune and stromal cell populations. This subset showed increased expression of both immune suppressor and immune effector genes compared to other GBMs and was enriched for the mesenchymal molecular subtype. Survival analyses suggested that tumor microenvironment infiltration pattern was an independent prognostic factor for GBM patients. Among all, patients with the mesenchymal subtype with low immune and stromal infiltration had the poorest survival. By combining molecular subtyping with gene expression measures of tumor infiltration, the present work contributes with improving prognostic models in GBM.
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spelling pubmed-71911882020-05-01 Improved prognostication of glioblastoma beyond molecular subtyping by transcriptional profiling of the tumor microenvironment Jeanmougin, Marine Håvik, Annette B. Cekaite, Lina Brandal, Petter Sveen, Anita Meling, Torstein R. Ågesen, Trude H. Scheie, David Heim, Sverre Lothe, Ragnhild A. Lind, Guro E. Mol Oncol Research Articles Glioblastoma (GBM), the most aggressive form of brain cancer, is characterized by a high level of molecular heterogeneity, and infiltration by various immune and stromal cell populations. Important advances have been made in deciphering the microenvironment of GBMs, but its association with existing molecular subtypes and its potential prognostic role remain elusive. We have investigated the abundance of infiltrating immune and stromal cells in silico, from gene expression profiles. Two cohorts, including in‐house normal brain and glioma samples (n = 70) and a large sample set from TCGA (n = 393), were combined into a single exploratory dataset. A third independent cohort (n = 124) was used for validation. Tumors were clustered based on their microenvironment infiltration profiles, and associations with known GBM molecular subtypes and patient outcome were tested a posteriori in a multivariable setting. We identified a subset of GBM samples with significantly higher abundances of most immune and stromal cell populations. This subset showed increased expression of both immune suppressor and immune effector genes compared to other GBMs and was enriched for the mesenchymal molecular subtype. Survival analyses suggested that tumor microenvironment infiltration pattern was an independent prognostic factor for GBM patients. Among all, patients with the mesenchymal subtype with low immune and stromal infiltration had the poorest survival. By combining molecular subtyping with gene expression measures of tumor infiltration, the present work contributes with improving prognostic models in GBM. John Wiley and Sons Inc. 2020-04-04 2020-05 /pmc/articles/PMC7191188/ /pubmed/32171051 http://dx.doi.org/10.1002/1878-0261.12668 Text en © 2020 The Authors. Published by FEBS Press and John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Jeanmougin, Marine
Håvik, Annette B.
Cekaite, Lina
Brandal, Petter
Sveen, Anita
Meling, Torstein R.
Ågesen, Trude H.
Scheie, David
Heim, Sverre
Lothe, Ragnhild A.
Lind, Guro E.
Improved prognostication of glioblastoma beyond molecular subtyping by transcriptional profiling of the tumor microenvironment
title Improved prognostication of glioblastoma beyond molecular subtyping by transcriptional profiling of the tumor microenvironment
title_full Improved prognostication of glioblastoma beyond molecular subtyping by transcriptional profiling of the tumor microenvironment
title_fullStr Improved prognostication of glioblastoma beyond molecular subtyping by transcriptional profiling of the tumor microenvironment
title_full_unstemmed Improved prognostication of glioblastoma beyond molecular subtyping by transcriptional profiling of the tumor microenvironment
title_short Improved prognostication of glioblastoma beyond molecular subtyping by transcriptional profiling of the tumor microenvironment
title_sort improved prognostication of glioblastoma beyond molecular subtyping by transcriptional profiling of the tumor microenvironment
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191188/
https://www.ncbi.nlm.nih.gov/pubmed/32171051
http://dx.doi.org/10.1002/1878-0261.12668
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