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Fig. 1 | Acta Neuropathologica Communications

Fig. 1

From: Translocator protein (18kDA) (TSPO) marks mesenchymal glioblastoma cell populations characterized by elevated numbers of tumor-associated macrophages

Fig. 1

TSPO mRNA expression in malignant gliomas is inversely correlated with promotor methylation. TSPO mRNA expression (RPKM) was analyzed in a TCGA-GBM and TCGA-LGG in silico data set (a-c). TSPO expression was analyzed based on WHO grades (WHO 2: 18 IDH-wt, 188 IDH-mut; WHO 3: 66 IDH-wt, 161 IDH-mut; WHO 4: 127 IDH-wt, 6 IDH-mut). Post-hoc Games Howell test revealed a significant increase of TSPO expression in WHO grade 4 gliomas (***p < 0.001) in comparison to WHO grade 2 and 3 (a). Analysis based on IDH mutation status (IDH-mut: 355, IDH-wt: 211) showed a significantly higher TSPO expression in IDH-wt gliomas compared to IDH-mut gliomas (Mann Whitney U, ***p ≤ 0.001) (b). Comparing expression subtypes of WHO grade 4 GBMs (MES: 56 IDH-wt; CL: 43 IDH-wt; PRO: 12 IDH-wt, 4 IDH-mut) TSPO expression was significantly higher in mesenchymal GBMs than in classical and proneural GBMs (Post Hoc Games Howell, **p < 0.01) (c). A schematic diagram of TSPO promotor CpG island location on Ensembl GRCh38 reference genome covered by seven probes (a-g) on the Infinium® HumanMethylation450 Bead Chip and their distance to the TSS of the TSPO main transcript ENST00000337554 (d). Statistical methylation analysis (Post Hoc Games Howell) of Beta values was performed with the TCGA-GBM and TCGA-LGG cohort for probe cg00343092 (marked in red) revealing significantly lower methylation levels in GBM (n = 130) compared to all other groups (AA: n = 129, NOS A: n = 62, AOD; n = 79, NOS OD: n = 118 and MG: n = 130) (e). Mean TSPO CpG island methylation on probe cg00343092 (Beta value) and mean TSPO mRNA expression (RPKM) show an inverse correlation (f). Spearman rho correlation of each matched value (n = 209) shows a significant inverse correlation (r = − 0.5548, ***p < 0.001) between methylation (probe cg00343092) and TSPO mRNA expression (g). Significances are displayed as follows: p > 0.05 = n.s., p < 0.05 = *, p < 0.01 = **, p < 0.001 = ***. CL: classical, CpG: 5’-C-phosphate-G-3’, IDH: isocitrate dehydrogenase, IDH-wt: IDH-wildtype, IDH-mut: IDH-mutant, GBM: glioblastoma, LGG: low-grade glioma, MES: mesenchymal, PRO: proneural, RPKM: reads per kilobase per million, TCGA: The Cancer Genome Atlas, TSS: transcription start site, AA: anaplastic astrocytoma WHO grade 3, NOS: not otherwise specified glioma WHO grade 2, AOD: anaplastic oligodendroglioma WHO grade 3, NOS OD: not otherwise specified oligodendroglioma WHO grade 2, MG: mixed glioma

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