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. 2021 Jun 23;12:3895. doi: 10.1038/s41467-021-23995-z

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© The Author(s) 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 6 — a Bar plot representing the top 20 predictors of glioblastoma overall survival in decreasing order of importance computed by the random forest classifier. Red triangles highlight HSPC subsets. Inset, Brier score indicates error rate of random forest classifier results as function of survival time (Brier score 0 = 0 % error, 1 = 100% error). MGMT O(6)-Methylguanine-DNA methyltransferase, G-CIMP Glioma CpG island methylator phenotype, IDH Isocitrate dehydrogenase. Source data are provided as a Source Data file. b Mortality rate as a function of hematopoietic stem cell (HSC) odds ratios derived by Syllogist and used to determine threshold separating HSC^high (n = 63) and HSC^low (n = 76) patients. Red lines represent 95% CI. c Kaplan–Meier plot of HSC^high and HSC^low patients using the threshold T = 0.54 selected from (b). Two-tailed logrank test. d Univariate Cox regression analysis of selected variables for overall survival and progression-free survival data. e Multivariable Cox proportional hazards model of the HSC subset and potential confounders (Age, MGMT methylation, and IDH mutations) for overall and progression-free survival. In (d) and (e), we used a two-tailed likelihood-ratio test corrected by the Benjamini–Hochberg procedure. All variables satisfied the proportionality hazards assumption (Methods). CMP Common myeloid progenitor, GMP Granulocyte–Monocyte progenitor, MEP Megakaryocyte–Erythroid progenitor. f Boxplots represent the expression of pro- and anti-inflammatory cytokines in HSC^high (n = 73) and HSC^low (n = 92) patient samples. TGFB1 Transforming growth factor beta 1, IL10, IL2 Interleukin 10 and 2, INFG Interferon gamma, TNF Tumor necrosis factor, IL12A Interleukin 12 subunit alpha, IL17A Interleukin 17A. g Boxplots represent the expression of the immune checkpoint markers PD-1 (PDCD1), PD-L1 (CD274), and PD-L2 (PDCD1LG2) in HSC^high and HSC^low samples. h Boxplots represent the expression of hematopoietic stem cell niche factors C-X-C motif chemokine 12 (CXCL12), leptin receptor (LEPR), and fibronectin (FN1) in HSC^high and HSC^low samples. In (f–h), boxplots are drawn with boxes representing the interquartile range (IQR), a line across the box indicating the median, and whiskers indicating 1.5 × IQR. Outliers are shown as closed dots. p values determined using a two-tailed Wilcoxon–Mann–Whitney U test corrected with the Benjamini–Hochberg procedure.