Glioblastoma TCGA Mesenchymal and IGS 23 Tumors are Identifiable by IHC and have an Immune-phenotype Indicating a Potential Benefit from Immunotherapy.

Biomarkers, Tumor / genetics Brain Neoplasms / classification Computational Biology Follow-Up Studies Glioblastoma / classification Humans Immunohistochemistry / methods Immunophenotyping / methods Mesoderm / pathology Oncogene Proteins, Fusion / genetics Prognosis RNA-Seq Retrospective Studies Tissue Array Analysis

Journal

Clinical cancer research : an official journal of the American Association for Cancer Research

ISSN: 1557-3265

Titre abrégé: Clin Cancer Res

Pays: United States

ID NLM: 9502500

Informations de publication

Date de publication:
15 12 2020

Historique:

received: 16 06 2020

revised: 29 07 2020

accepted: 24 09 2020

pubmed: 2 10 2020

medline: 15 12 2021

entrez: 1 10 2020

Statut: ppublish

Résumé

Molecular subtype classifications in glioblastoma may detect therapy sensitivities. IHC would potentially allow the identification of molecular subtypes in routine clinical practice. Formalin-fixed, paraffin-embedded tumor samples of 124 uniformly treated, newly diagnosed patients with glioblastoma were submitted to RNA sequencing, IHC, and immune-phenotyping to identify differences in molecular subtypes associated with treatment sensitivities. We detected high molecular and IHC overlapping of the The Cancer Genome Atlas (TCGA) mesenchymal subtype with instrinsic glioma subtypes (IGS) cluster 23 and of the TCGA classical subtype with IGS cluster 18. IHC patterns, gene fusion profiles, and immune-phenotypes varied across subtypes. IHC revealed that the TCGA classical subtype was identified by high expression of EGFR and low expression of PTEN, while the mesenchymal subtype was identified by low expression of SOX2 and high expression of two antibodies, SHC1 and TCIRG1, selected on the basis of RNA differential transcriptomic expression. The proneural subtype was identified by frequent positive IDH1 expression and high Olig2 and Ki67 expression. Immune-phenotyping showed that mesenchymal and IGS 23 tumors exhibited a higher positive effector cell score, a higher negative suppressor cell score, and lower levels of immune checkpoint molecules. The cell-type deconvolution analysis revealed that these tumors are highly enriched in M2 macrophages, resting memory CD4 There is a subset of tumors, frequently classified as mesenchymal or IGS cluster 23, that may be identified with IHC and could well be optimal candidates for immunotherapy.

Identifiants

DOI: 10.1158/1078-0432.CCR-20-2171 PMID: 32998960

pubmed: 32998960

pii: 1078-0432.CCR-20-2171

doi: 10.1158/1078-0432.CCR-20-2171

doi:

Substances chimiques

Biomarkers, Tumor 0

Oncogene Proteins, Fusion 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

6600-6609

Informations de copyright

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