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Cell-lines and immune classification of glioblastoma define patient’s prognosis

Abstract

Background:

Prognostic markers for glioblastoma are lacking. Both intrinsic tumor 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 glioma 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. Transcriptomic profiles of pure immune cells were used to generate a signature for each immune cells. Presence of subtypes of glioblastoma cell-lines and immune cells was determined using deconvolution.

Results:

Glioblastoma cell-lines classification defined 3 new molecular groups called Oncogenic, Metabolic and Neuronal Communication-enriched. Neuronal Communication-enriched tumors were associated with poor prognosis in both cohorts. Immune cell infiltrate was more frequent in Mesenchymal classical classification subgroup and Metabolic-enriched tumors. Myeloid infiltrate, B cells and regulatory T cells are the main components of the immune infiltrate. No immune cell infiltrate was associated with prognosis in neither of the two cohorts. However, 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.

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