Cell lines and immune classification of glioblastoma define patient's prognosis.


Journal

British journal of cancer
ISSN: 1532-1827
Titre abrégé: Br J Cancer
Pays: England
ID NLM: 0370635

Informations de publication

Date de publication:
04 2019
Historique:
received: 25 09 2018
accepted: 28 01 2019
revised: 11 01 2019
pubmed: 23 3 2019
medline: 28 2 2020
entrez: 23 3 2019
Statut: ppublish

Résumé

Prognostic markers for glioblastoma are lacking. Both intrinsic tumour characteristics and microenvironment could influence cancer prognostic. The aim of our study was to generate a pure glioblastoma cell lines and immune classification in order to decipher the respective role of glioblastoma cell and microenvironment on prognosis. We worked on two large cohorts of patients suffering from glioblastoma (TCGA, n = 481 and Rembrandt, n = 180) for which clinical data, transcriptomic profiles and outcome were recorded. Transcriptomic profiles of 129 pure glioblastoma cell lines were clustered to generate a glioblastoma cell lines classification. Presence of subtypes of glioblastoma cell lines and immune cells was determined using deconvolution. Glioblastoma cell lines classification defined three new molecular groups called oncogenic, metabolic and neuronal communication enriched. Neuronal communication-enriched tumours were associated with poor prognosis in both cohorts. Immune cell infiltrate was more frequent in mesenchymal classical classification subgroup and metabolic-enriched tumours. A combination of age, glioblastoma cell lines classification and immune classification could be used to determine patient's outcome in both cohorts. Our study shows that glioblastoma-bearing patients can be classified based on their age, glioblastoma cell lines classification and immune classification. The combination of these information improves the capacity to address prognosis.

Sections du résumé

BACKGROUND
Prognostic markers for glioblastoma are lacking. Both intrinsic tumour characteristics and microenvironment could influence cancer prognostic. The aim of our study was to generate a pure glioblastoma cell lines and immune classification in order to decipher the respective role of glioblastoma cell and microenvironment on prognosis.
METHODS
We worked on two large cohorts of patients suffering from glioblastoma (TCGA, n = 481 and Rembrandt, n = 180) for which clinical data, transcriptomic profiles and outcome were recorded. Transcriptomic profiles of 129 pure glioblastoma cell lines were clustered to generate a glioblastoma cell lines classification. Presence of subtypes of glioblastoma cell lines and immune cells was determined using deconvolution.
RESULTS
Glioblastoma cell lines classification defined three new molecular groups called oncogenic, metabolic and neuronal communication enriched. Neuronal communication-enriched tumours were associated with poor prognosis in both cohorts. Immune cell infiltrate was more frequent in mesenchymal classical classification subgroup and metabolic-enriched tumours. A combination of age, glioblastoma cell lines classification and immune classification could be used to determine patient's outcome in both cohorts.
CONCLUSIONS
Our study shows that glioblastoma-bearing patients can be classified based on their age, glioblastoma cell lines classification and immune classification. The combination of these information improves the capacity to address prognosis.

Identifiants

pubmed: 30899088
doi: 10.1038/s41416-019-0404-y
pii: 10.1038/s41416-019-0404-y
pmc: PMC6474266
doi:

Substances chimiques

Neoplasm Proteins 0

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

806-814

Références

Weller, M. et al. European Association for Neuro-Oncology (EANO) guideline on the diagnosis and treatment of adult astrocytic and oligodendroglial gliomas. Lancet Oncol. 18, e315–e329 (2017).
doi: 10.1016/S1470-2045(17)30194-8
Verhaak, R. G. W. et al. Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell. 17, 98–110 (2010).
doi: 10.1016/j.ccr.2009.12.020
Huse, J. T., Phillips, H. S. & Brennan, C. W. Molecular subclassification of diffuse gliomas: seeing order in the chaos. Glia 59, 1190–1199 (2011).
doi: 10.1002/glia.21165
Phillips, H. S. et al. Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis. Cancer Cell. 9, 157–173 (2006).
doi: 10.1016/j.ccr.2006.02.019
Zheng, S., Chheda, M. G. & Verhaak, R. G. W. Studying a complex tumour: potential and pitfalls. Cancer J. Sudbury Mass. 18, 107–114 (2012).
doi: 10.1097/PPO.0b013e3182431c57
Olar, A. & Aldape, K. D. Using the molecular classification of glioblastoma to inform personalized treatment. J. Pathol. 232, 165–177 (2014).
doi: 10.1002/path.4282
Fecci, P. E. et al. Increased regulatory T-cell fraction amidst a diminished CD4 compartment explains cellular immune defects in patients with malignant glioma. Cancer Res. 66, 3294–3302 (2006).
doi: 10.1158/0008-5472.CAN-05-3773
Lohr, J. et al. Effector T-cell infiltration positively impacts survival of glioblastoma patients and is impaired by tumour-derived TGF-β. Clin. Cancer Res. J. Am. Assoc. Cancer Res. 17, 4296–4308 (2011).
doi: 10.1158/1078-0432.CCR-10-2557
Alexiou, G. A. et al. Circulating progenitor cells: a comparison of patients with glioblastoma or meningioma. Acta Neurol. Belg. 113, 7–11 (2013).
doi: 10.1007/s13760-012-0097-y
Wainwright, D. A., Dey, M., Chang, A. & Lesniak, M. S. Targeting Tregs in malignant brain cancer: overcoming IDO. Front. Immunol. 4, 116 (2013).
doi: 10.3389/fimmu.2013.00116
Madkouri, R. et al. Immune classifications with cytotoxic CD8 + and Th17 infiltrates are predictors of clinical prognosis in glioblastoma. Oncoimmunology https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5486170/ (2017).
Charoentong, P. et al. Pan-cancer immunogenomic analyses reveal genotype-immunophenotype relationships and predictors of response to checkpoint blockade. Cell Rep. 18, 248–262 (2017).
doi: 10.1016/j.celrep.2016.12.019
Shen-Orr, S. S. & Gaujoux, R. Computational deconvolution: extracting cell type-specific information from heterogeneous samples. Curr. Opin. Immunol. 25, 571–578 (2013).
doi: 10.1016/j.coi.2013.09.015
Abbas, A. R., Wolslegel, K., Seshasayee, D., Modrusan, Z. & Clark, H. F. Deconvolution of blood microarray data identifies cellular activation patterns in systemic lupus erythematosus. PLoS ONE 4, e6098 (2009).
doi: 10.1371/journal.pone.0006098
Gong, T. et al. Optimal deconvolution of transcriptional profiling data using quadratic programming with application to complex clinical blood samples. PLoS ONE 6, e27156 (2011).
doi: 10.1371/journal.pone.0027156
Qiao, W. et al. PERT: a method for expression deconvolution of human blood samples from varied microenvironmental and developmental conditions. PLoS Comput. Biol. 8, e1002838 (2012).
doi: 10.1371/journal.pcbi.1002838
Liebner, D. A., Huang, K. & Parvin, J. D. MMAD: microarray microdissection with analysis of differences is a computational tool for deconvoluting cell type-specific contributions from tissue samples. Bioinformatics 30, 682–689 (2014).
doi: 10.1093/bioinformatics/btt566
Zhong, Y., Wan, Y.-W., Pang, K., Chow, L. M. L. & Liu, Z. Digital sorting of complex tissues for cell type-specific gene expression profiles. BMC Bioinform. 14, 89 (2013).
doi: 10.1186/1471-2105-14-89
Zuckerman, N. S., Noam, Y., Goldsmith, A. J. & Lee, P. P. A self-directed method for cell-type identification and separation of gene expression microarrays. PLoS Comput. Biol. 9, e1003189 (2013).
doi: 10.1371/journal.pcbi.1003189
Barrett, T. et al. NCBI GEO: archive for functional genomics data sets--update. Nucleic Acids Res. 41, D991–D995 (2013)..
doi: 10.1093/nar/gks1193
Davis, S. & Meltzer, P. S. GEOquery: a bridge between the Gene Expression Omnibus (GEO) and BioConductor. Bioinforma. Oxf. Engl. 23, 1846–1847 (2007).
doi: 10.1093/bioinformatics/btm254
Brennan, C. W. et al. The somatic genomic landscape of glioblastoma. Cell 155, 462–477 (2013).
doi: 10.1016/j.cell.2013.09.034
Wan, Y.-W., Allen, G. I. & Liu, Z. TCGA2STAT: simple TCGA data access for integrated statistical analysis in R. Bioinforma. Oxf. Engl. 32, 952–954 (2016).
doi: 10.1093/bioinformatics/btv677
Madhavan, S. et al. Rembrandt: helping personalized medicine become a reality through integrative translational research. Mol. Cancer Res. 7, 157–167 (2009).
Gautier, L., Cope, L., Bolstad, B. M. & Irizarry, R. A. affy—analysis of Affymetrix GeneChip data at the probe level. Bioinformatics 20, 307–15 (2004).
doi: 10.1093/bioinformatics/btg405
Leek, J. T., Johnson, W. E., Parker, H. S., Jaffe, A. E. & Storey, J. D. The sva package for removing batch effects and other unwanted variation in high-throughput experiments. Bioinforma. Oxf. Engl. 28, 882–883 (2012).
doi: 10.1093/bioinformatics/bts034
Ritchie, M. E. et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 43, e47 (2015).
doi: 10.1093/nar/gkv007
Kuleshov, M. V. et al. Enrichr: a comprehensive gene set enrichment analysis web server 2016 update. Nucleic Acids Res. 44, W90–W97 (2016).
doi: 10.1093/nar/gkw377
Newman, A. M. et al. Robust enumeration of cell subsets from tissue expression profiles. Nat. Methods 12, 453–457 (2015).
doi: 10.1038/nmeth.3337
Josse J., Le S. & Mazet J. FactoMineR: multivariate exploratory data analysis and data mining. https://CRAN.R-project.org/package=FactoMineR (2018).
Kassambara A. & Mundt F. factoextra: extract and visualize the results of multivariate data analyses. https://CRAN.R-project.org/package=factoextra (2017).
Friedman, J. et al. glmnet: Lasso and elastic-net regularized generalized linear models. https://CRAN.R-project.org/package=glmnet (2018).
Cooper, L. A. D. et al. The proneural molecular signature is enriched in oligodendrogliomas and predicts improved survival among diffuse gliomas. PLoS ONE 5, e12548 (2010).
doi: 10.1371/journal.pone.0012548
Wang, Q. et al. Tumour evolution of glioma-intrinsic gene expression subtypes associates with immunological changes in the microenvironment. Cancer Cell. 33, 152 (2018).
doi: 10.1016/j.ccell.2017.12.012
Han, S. et al. Tumour-infiltrating CD4(+) and CD8(+) lymphocytes as predictors of clinical outcome in glioma. Br. J. Cancer 110, 2560–2568 (2014).
doi: 10.1038/bjc.2014.162
Mohme, M. et al. Immunophenotyping of newly diagnosed and recurrent glioblastoma defines distinct immune exhaustion profiles in peripheral and tumour-infiltrating lymphocytes. Clin. Cancer Res. 24, 4187–4200 (2018). https://doi.org/10.1158/1078-0432.CCR-17-2617 .
doi: 10.1158/1078-0432.CCR-17-2617
Tcyganov, E., Mastio, J., Chen, E. & Gabrilovich, D. I. Plasticity of myeloid-derived suppressor cells in cancer. Curr. Opin. Immunol. 51, 76–82 (2018).
doi: 10.1016/j.coi.2018.03.009
Lim, M., Xia, Y., Bettegowda, C. & Weller, M. Current state of immunotherapy for glioblastoma. Nat. Rev. Clin. Oncol. 15, 422–442 (2018).
doi: 10.1038/s41571-018-0003-5
Di Carlo D. T., Cagnazzo F., Benedetto N., Morganti R. & Perrini P. Multiple high-grade gliomas: epidemiology, management, and outcome. A systematic review and meta-analysis. Neurosurg. Rev. (2017). https://doi.org/10.1007/s10143-017-0928-7 .
Hegi, M. E. et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. N. Engl. J. Med. 352, 997–1003 (2005).
doi: 10.1056/NEJMoa043331
Paldor I., Drummond K. J. & Kaye A. H. IDH1 mutation may not be prognostically favorable in glioblastoma when controlled for tumour location: a case-control study. J. Clin. Neurosci. 34, 117–120 (2016).
Labussière, M. et al. TERT promoter mutations in gliomas, genetic associations and clinico-pathological correlations. Br. J. Cancer 111, 2024–2032 (2014).
doi: 10.1038/bjc.2014.538

Auteurs

Quentin Klopfenstein (Q)

Research Platform in Biological Oncology, Dijon, France.
GIMI Genetic and Immunology Medical Institute, Dijon, France.

Caroline Truntzer (C)

Research Platform in Biological Oncology, Dijon, France.
GIMI Genetic and Immunology Medical Institute, Dijon, France.

Julie Vincent (J)

Department of Medical Oncology, Centre GF Leclerc, Dijon, France.

Francois Ghiringhelli (F)

Research Platform in Biological Oncology, Dijon, France. fghiringhelli@cgfl.fr.
GIMI Genetic and Immunology Medical Institute, Dijon, France. fghiringhelli@cgfl.fr.
Department of Medical Oncology, Centre GF Leclerc, Dijon, France. fghiringhelli@cgfl.fr.
INSERM, UMR1231, Dijon, France. fghiringhelli@cgfl.fr.

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