American Association for Cancer Research
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Figure SF5 from Regulatory Network of PD1 Signaling Is Associated with Prognosis in Glioblastoma Multiforme

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journal contribution
posted on 2023-04-01, 00:20 authored by Camila M. Lopes-Ramos, Tatiana Belova, Tess H. Brunner, Marouen Ben Guebila, Daniel Osorio, John Quackenbush, Marieke L. Kuijjer

A) Comparison of distributions of immune scores from xCell between the two survival groups in the discovery and validation datasets. In the boxplots, boxes represent the median and first and third quantiles, whiskers represent 1.5Ã-IQR. B) Association of the immune scores with PD1 targeting scores in the discovery and validation datasets. Regression lines with confidence intervals of 0.95 are shown for the long-term (blue) and short-term (red) groups.


National Cancer Institute (NCI)

United States Department of Health and Human Services

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H2020 Marie Skłodowska-Curie Actions (MSCA)



Glioblastoma is an aggressive cancer of the brain and spine. While analysis of glioblastoma ‘omics data has somewhat improved our understanding of the disease, it has not led to direct improvement in patient survival. Cancer survival is often characterized by differences in gene expression, but the mechanisms that drive these differences are generally unknown. We therefore set out to model the regulatory mechanisms associated with glioblastoma survival. We inferred individual patient gene regulatory networks using data from two different expression platforms from The Cancer Genome Atlas. We performed comparative network analysis between patients with long- and short-term survival. Seven pathways were identified as associated with survival, all of them involved in immune signaling; differential regulation of PD1 signaling was validated to correspond with outcome in an independent dataset from the German Glioma Network. In this pathway, transcriptional repression of genes for which treatment options are available was lost in short-term survivors; this was independent of mutational burden and only weakly associated with T-cell infiltration. Collectively, these results provide a new way to stratify patients with glioblastoma that uses network features as biomarkers to predict survival. They also identify new potential therapeutic interventions, underscoring the value of analyzing gene regulatory networks in individual patients with cancer. Genome-wide network modeling of individual glioblastomas identifies dysregulation of PD1 signaling in patients with poor prognosis, indicating this approach can be used to understand how gene regulation influences cancer progression.

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