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Fig. 7 | Acta Neuropathologica Communications

Fig. 7

From: Identifying new biomarkers of aggressive GroupĀ 3 and SHH medulloblastoma using 3D hydrogel models, single cell RNA sequencing and 3D OrbiSIMS imaging

Fig. 7

HR-MAS NMR spectroscopy detected fumarate levels group 3 and high LUM gene expression levels in SHH MB patients predict better overall survival. HR-MAS NMR spectroscopy analysis of fumarate in SHH (a, nā€‰=ā€‰13) and Group 3 (b, nā€‰=ā€‰16) patients indicates no survival difference for SHH patients (no fumarate detected nā€‰=ā€‰8; fumarate detected nā€‰=ā€‰5) but a strong trend for worse overall survival in Group 3 patients (no fumarate detected nā€‰=ā€‰12; fumarate detected nā€‰=ā€‰4) with detectable fumarate levels. c Genomic analysis of LUM expression in SHH (c; logrank test, pā€‰<ā€‰0.001) and Group 3 (d; logrank test, pā€‰=ā€‰0.056) patients identified that high LUM expression correlates with better overall survival than low LUM expression, whereas the opposite trend is true in Group 3 patients. e A graphical abstract of this study illustrating that by using by using a combination of state-of-the-art techniques (scRNAseq and 3D OrbiSIMS), in a realistic 3D model, we have identified sub-group-specific tumour phenotypes in SHH and Group 3 medulloblastoma. In the SHH sub-group we have demonstrated the formation of an ECM shell-like structure composed of laminin, type I- and VI-collagens and lumican that can be used to identify low-risk SHH tumours. This could facilitate more accurate risk stratification of SHH medulloblastoma. In the Group 3 sub-group we have shown that fumarate accumulation identifies very-high risk patients that could benefit from a chemotherapy combination with NRF2 targeted therapy approaches

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