Article Figures & Data
Figures
- 1
Differentially expressed genes between GBM and normal brain tissues. (A) Volcano plots showing the log2 (fold change) of mRNA in GBM compared to normal brain tissues, and the correspondinglog10 (adjusted P value) in TCGA, GSE4290 and GSE16011 datasets. Genes with adjusted P value below 0.05 and fold change above 2 (below -2) were marked with red (blue) dots. (B) Venn diagrams showing the gene numbers of the upregulated genes (left) and the downregulated genes (right) of GBM in TCGA, GSE4290 and GSE16011 cohorts. (C) Heatmaps of the overlapped genes in TCGA, GSE4290 and GSE16011 datasets. The overlapped genes that are from Figure 1B include 483 upregulated genes and 765 downregulated genes.
- 2
The four-gene signature-derived risk score is high in GBM. (A) The calculation formula and the value of risk score (top), the corresponding expression of four key genes (middle), and the associated clinicopathological parameters (bottom). ߔ indicates the regression coefficient derived from multivariate COX stepwise regression in TCGA GBM cohort; E represents the expression value of the corresponding gene. The P-value indicates the correlation between the risk score and the clinicopathological parameters (Supplementary Table S5). KPS, Karnofsky performance status; IDH, isocitrate dehydrogenase; MGMT, O(6)-methylguanine-DNA methyltransferase; NA, not available. (B-D) Risk scores in GBM and normal brain tissues (B), in IDH-wt GBM and IDH-mut GBM (C), and in mesenchymal GBM and non-mesenchymal (proneural and classical) GBM (D) in TCGA GBM cohort. IDH, isocitrate dehydrogenase; IDH-wt, IDH-wild type; IDH-mut, IDH-mutation. Data are shown as mean ± SEM, *P < 0.05, *** P < 0.001, ns, not significant.
- S1
Survival analysis of GBM patients. (A-B) Kaplan-Meier overall survival analysis of GBM patients stratified by IDH status (A), and expression subtypes (B). IDH, isocitrate dehydrogenase; IDH-wt, IDH-wild type; IDH-mut, IDH-mutation. Mes, mesenchymal; Non-Mes, non-mesenchymal, including proneural and classical subtypes.
- 3
Risk score predicts the prognosis and treatment response in TCGA GBM cohort. (A-C) KaplanMeier overall survival analysis among TCGA GBM patients stratified by risk score only (A), combined with IDH status (B), and combined with expression subtypes (C). Mes, mesenchymal; Non-Mes, non-mesenchymal, including proneural and classical subtypes. (D-E) KaplanMeier overall survival analysis of TCGA GBM patients with TMZ chemotherapy (D), or radiotherapy (E) according to the risk score. TMZ, temozolomide.
- 4
Performance of risk score in predicting the survival and treatment response in independent GEO GBM cohorts. (A) Comparison of risk scores between GBM and normal brain tissues in GSE4290, GSE16011, GSE59612 and GSE90604. (B) Kaplan-Meier overall survival analysis of high-risk and low-risk GBM patients in GSE16011, GSE43378 and GSE83300. (C) Kaplan-Meier overall survival analysis of GBM patients with radiotherapy in GSE16011 according to the risk score. (D) Risk scores in mesenchymal GBM and non-mesenchymal (proneural and classical) GBM (up), and KaplanMeier overall survival analysis of GBM patients stratified by risk scores combined with expression subtypes (down). Mes, mesenchymal; Non-Mes, non-mesenchymal, including proneural and classical subtypes. (E) Risk scores in IDH-wt GBM and IDH-mut GBM (up), and KaplanMeier overall survival analysis of GBM patients stratified by risk scores combined with IDH status (down). IDH, isocitrate dehydrogenase; IDH-wt, IDH-wild type; IDH-mut, IDH-mutation. Data are shown as mean ± SEM, *P < 0.05, ** P < 0.01, *** P < 0.001, ns, not significant.
- 5
Four-gene signature associated biological pathways in high-risk GBM. (A) Enrichment map showing the pathways enriched in high-risk GBM through GSEA analysis. Nodes represent enriched gene sets with P-value below 0.05. Node with deep red color correlates with small P-value. Node size corresponds to the number of genes within gene set. Edge thickness corresponds to the number of shared genes between gene sets. (B) Representative enriched pathways in high-risk GBM through GSEA analysis. NES, normalized enrichment score.
- 6
Validation of the differential expression of the four genes in GBM cells. (A and B) Western blot images (A) and the relevant quantification (B) of OSMR, HOXC10, SCARA3 and SLC39A10 in GBM cell line LN229, primary GBM cells (GBM-1 and GBM-2), and normal glial cell line HEB. The relative expression of target proteins is quantified in comparison with ݭActin and normalized to the corresponding expression in HEB cells. Data are shown as mean ± SEM from three independent experiments, *P < 0.05, ** P < 0.01, *** P < 0.001.
Tables
Sample ID (normal) Sample ID (GBM) Sample ID (GBM) Sample ID (GBM) Sample ID (GBM) Sample ID (GBM) TCGA-06-0675-11 TCGA-02-0047-01 TCGA-06-0646-01 TCGA-06-5856-01 TCGA-19-1389-02 TCGA-28-2513-01 TCGA-06-0678-11 TCGA-02-0055-01 TCGA-06-0649-01 TCGA-06-5858-01 TCGA-19-1390-01 TCGA-28-2514-01 TCGA-06-0680-11 TCGA-02-2483-01 TCGA-06-0686-01 TCGA-06-5859-01 TCGA-19-1787-01 TCGA-28-5204-01 TCGA-06-0681-11 TCGA-02-2485-01 TCGA-06-0743-01 TCGA-08-0386-01 TCGA-19-2619-01 TCGA-28-5207-01 TCGA-06-AABW-11 TCGA-02-2486-01 TCGA-06-0744-01 TCGA-12-0616-01 TCGA-19-2620-01 TCGA-28-5208-01 TCGA-06-0125-01 TCGA-06-0745-01 TCGA-12-0618-01 TCGA-19-2624-01 TCGA-28-5209-01 TCGA-06-0125-02 TCGA-06-0747-01 TCGA-12-0619-01 TCGA-19-2625-01 TCGA-28-5213-01 TCGA-06-0129-01 TCGA-06-0749-01 TCGA-12-0821-01 TCGA-19-2629-01 TCGA-28-5215-01 TCGA-06-0130-01 TCGA-06-0750-01 TCGA-12-1597-01 TCGA-19-4065-01 TCGA-28-5216-01 TCGA-06-0132-01 TCGA-06-0878-01 TCGA-12-3650-01 TCGA-19-4065-02 TCGA-28-5218-01 TCGA-06-0138-01 TCGA-06-0882-01 TCGA-12-3652-01 TCGA-19-5960-01 TCGA-28-5220-01 TCGA-06-0141-01 TCGA-06-1804-01 TCGA-12-3653-01 TCGA-26-1442-01 TCGA-32-1970-01 TCGA-06-0152-02 TCGA-06-2557-01 TCGA-12-5295-01 TCGA-26-5132-01 TCGA-32-1980-01 TCGA-06-0156-01 TCGA-06-2558-01 TCGA-12-5299-01 TCGA-26-5133-01 TCGA-32-1982-01 TCGA-06-0157-01 TCGA-06-2559-01 TCGA-14-0736-02 TCGA-26-5134-01 TCGA-32-2615-01 TCGA-06-0158-01 TCGA-06-2561-01 TCGA-14-0781-01 TCGA-26-5135-01 TCGA-32-2616-01 TCGA-06-0168-01 TCGA-06-2562-01 TCGA-14-0787-01 TCGA-26-5136-01 TCGA-32-2632-01 TCGA-06-0171-02 TCGA-06-2563-01 TCGA-14-0789-01 TCGA-26-5139-01 TCGA-32-2634-01 TCGA-06-0174-01 TCGA-06-2564-01 TCGA-14-0790-01 TCGA-27-1830-01 TCGA-32-2638-01 TCGA-06-0178-01 TCGA-06-2565-01 TCGA-14-0817-01 TCGA-27-1831-01 TCGA-32-4213-01 TCGA-06-0184-01 TCGA-06-2567-01 TCGA-14-0871-01 TCGA-27-1832-01 TCGA-32-5222-01 TCGA-06-0187-01 TCGA-06-2569-01 TCGA-14-1034-01 TCGA-27-1834-01 TCGA-41-2571-01 TCGA-06-0190-01 TCGA-06-2570-01 TCGA-14-1034-02 TCGA-27-1835-01 TCGA-41-2572-01 TCGA-06-0190-02 TCGA-06-5408-01 TCGA-14-1402-02 TCGA-27-1837-01 TCGA-41-3915-01 TCGA-06-0210-01 TCGA-06-5410-01 TCGA-14-1823-01 TCGA-27-2519-01 TCGA-41-4097-01 TCGA-06-0210-02 TCGA-06-5411-01 TCGA-14-1825-01 TCGA-27-2521-01 TCGA-41-5651-01 TCGA-06-0211-01 TCGA-06-5412-01 TCGA-14-1829-01 TCGA-27-2523-01 TCGA-76-4925-01 TCGA-06-0211-02 TCGA-06-5413-01 TCGA-14-2554-01 TCGA-27-2524-01 TCGA-76-4926-01 TCGA-06-0219-01 TCGA-06-5414-01 TCGA-15-0742-01 TCGA-27-2526-01 TCGA-76-4927-01 TCGA-06-0221-02 TCGA-06-5415-01 TCGA-15-1444-01 TCGA-27-2528-01 TCGA-76-4928-01 TCGA-06-0238-01 TCGA-06-5416-01 TCGA-16-0846-01 TCGA-28-1747-01 TCGA-76-4929-01 TCGA-06-0644-01 TCGA-06-5417-01 TCGA-16-1045-01 TCGA-28-1753-01 TCGA-76-4931-01 TCGA-06-0645-01 TCGA-06-5418-01 TCGA-19-0957-02 TCGA-28-2509-01 TCGA-76-4932-01 Characteristic GBM patients (n = 165) Gender Male 106 Female 59 Age =50 128 <50 37 Grade I-III 0 IV 165 KPS score =80 88 <80 36 Missing 41 IDH status Mutation 11 Wild type 142 Missing 12 MGMT status Methylated 58 Unmethylated 67 Missing 40 Expression subtypes Mesenchymal 48 Classical 68 Proneural 49 Radiotherapy Yes 127 No 4 Missing 34 Chemotherapy Yes 112 No 19 Missing 34 Characteristic GSE4290 GSE16011 GSE43378 GSE59612 GSE83300 GSE90604 Normal tissues 23 8 0 17 0 7 GBM cases 81 159 32 75 50 16 GBM_gender Male 108 20 44 24 10 Female 51 12 31 25 6 Missing 81 0 0 0 1 0 GBM_age =50 NA 107 22 67 19 NA <50 NA 52 10 8 31 NA GBM_grade I-III 0 0 0 0 0 0 IV 81 155 32 75 50 16 GBM_cases with survival NA 155 32 NA 50 NA NA, not available.
Notes:
(1) All the GBM cases in the above GEO datasets were included in our study except for 4 of 159 GBM cases in GSE16011 without survival information.
(2) The glioma samples but not GBM samples in GSE4290 (26 astrocytoma and 50 oligodendroglioma), GSE16011 (29 astrocytoma, 8 pilocytic astrocytoma, 52 oligodendroglioma and 28 mixed glioma) and GSE43378 (5 astrocytoma and 13 anaplastic oligodendroglioma) were not included in our study.
(3) In GSE90604, the data from 7 normal brain tissues were included while the data from 2 normal astrocyte cell lines were excluded in our study.
Cases Primary cells Gender Age Tumor location WHO grade Histology IDH status Case 1 GBM-1 Female 22 Right temporal, parietal and occipital lobe IV Glioblastoma Wild type Case 2 GBM-2 Female 37 Left temporal and parietal lobe IV Glioblastoma Wild type Gene name Up/Down Univariate analysis Multivariate analysis HR (95%CI) P HR (95%CI) P OSMR UP 0.312 1.366 (1.181, 1.581) < 0.001 0.279 1.321 (1.136, 1.537) < 0.001 PDIA4 UP 0.511 1.667 (1.246, 2.231) 0.001 GJB2 UP 0.151 1.164 (1.063, 1.273) 0.001 FKBP9 UP 0.320 1.378 (1.135, 1.672) 0.001 STEAP3 UP 0.222 1.248 (1.086, 1.434) 0.002 HOXC10 UP 0.100 1.105 (1.037, 1.177) 0.002 0.089 1.093 (1.024, 1.167) 0.008 ISG20 UP 0.297 1.346 (1.112, 1.629) 0.002 SCARA3 UP 0.337 1.401 (1.127, 1.742) 0.002 0.238 1.268 (1.018, 1.580) 0.034 ZNF540 Down 0.348 0.706 (0.558, 0.893) 0.004 IKBIP UP 0.404 1.498 (1.131, 1.984) 0.005 KDELC2 UP 0.326 1.385 (1.104, 1.738) 0.005 SPAG4 UP 0.160 1.174 (1.048, 1.315) 0.006 C1RL UP 0.216 1.241 (1.065, 1.446) 0.006 SLC39A10 Down 0.494 0.611 (0.430, 0.868) 0.006 0.424 0.655 (0.445, 0.963) 0.031 GNS UP 0.456 1.578 (1.140, 2.185) 0.006 KHDRBS2 Down 0.147 0.863 (0.775, 0.961) 0.007 SLC2A10 UP 0.241 1.273 (1.062, 1.525) 0.009 DENND2A UP 0.263 1.301 (1.066, 1.588) 0.010 Abbreviations: ݬ regression coefficient; HR, hazard ratio; CI, confidence interval.
- S5
Correlation between the risk score and clinicopathological parameters in TCGA GBM cohort
Factor Risk score P value Low (n = 77) High (n = 88) Gender 0.633 Male 48 (62.3%) 58 (65.9%) Female 29 (37.7%) 30 (34.1%) Age 0.517 =50 58 (75.3%) 70 (79.5%) <50 19 (24.7%) 18 (20.5%) KPS score 0.124 =80 39 (50.6%) 49 (55.7%) <80 22 (28.6%) 14 (15.9%) Missing 16 (20.8%) 25 (28.4%) IDH status 0.004** Mutation 10 (13.0%) 1 (1.1%) Wild type 64 (83.1%) 78 (88.6%) Missing 3 (3.9%) 9 (10.2%) MGMT status 0.214 Methylated 28 (36.4%) 30 (34.1%) Unmethylated 35 (45.5%) 32 (36.4%) Missing 14 (18.2%) 26 (29.5%) Expression subtypes 0.028* Mesenchymal 16 (20.8%) 32 (36.4%) Non-mesenchymal 61 (79.2%) 56 (63.6%) Radiotherapy 0.180 Yes 62 (80.5%) 65 (73.9%) No 0 (0.0%) 4 (4.5%) Missing 15 (19.5%) 19 (21.6%) Chemotherapy 0.946 Yes 53 (68.8%) 59 (67.0%) No 9 (11.7%) 10 (11.4%) Missing 15 (19.5%) 19 (21.6%) KPS, Karnofsky performance status; IDH, isocitrate dehydrogenase; MGMT, O(6)-methylguanine-DNA methyltransferase. *, P < 0.05; **, P < 0.01.
- S6
Univariate and multivariate Cox regression analysis of clinicopathological parameters and risk score for overall survival in TCGA GBM cohort
Factor Univariate analysis Multivariate analysis HR (95%CI) P HR (95%CI) P Gender 0.995 (0.691, 1.432) 0.977 Age 1.029 (1.013, 1.044) < 0.001 1.034 (1.013, 1.055) 0.001 KPS score 0.893 (0.568, 1.405) 0.625 IDH status 0.229 (0.092, 0.568) 0.001 MGMT status 0.568 (0.368, 0.875) 0.010 0.600 (0.382, 0.941) 0.026 Expression subtypes 1.509 (1.015, 2.245) 0.042 Radiotherapy 0.467 (0.171, 1.279) 0.138 Chemotherapy 0.672 (0.396, 1.141) 0.141 Risk score 2.714 (1.924, 3.829) < 0.001 2.046 (1.321, 3.168) 0.001 KPS, Karnofsky performance status; IDH, isocitrate dehydrogenase; MGMT, O(6)-methylguanine-DNA methyltransferase; HR, hazard ratio; CI, confidence interval.
In this issue
Jump to section
Related Articles
Cited By...
- No citing articles found.