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. 2019 Feb 5;41:214–224. doi: 10.1016/j.ebiom.2019.01.052

Fig. 3.

Fig. 3

V-ATPase pump conformation resolves the heterogeneous class of LGG/IDHwt. a) Eight V-ATPase subunits were differentially expressed in LGG/IDHmut compared with GBM (p < 0·00001, and absolute Log2 ratio value >0·3; see Supplemental Table 10). Moreover, differential expression of these subunits was examined in LGG/IDHmut samples with respect to the presence/absence of the 1p19q co-deletion. ***, p < 0·0001; **, p = 0·001; *, p = 0·04; §, p = 0·006 (Kolmogorov–Smirnov test). Data are presented as box plots (lower, median and upper quartile) with whiskers indicating the 10 and 90 percentiles. c) Expression of V-ATPase subunit genes ATP6V1G2 and ATP6V1G1 in primary or recurrent LGG samples. Each dot represents one sample. *, p = 0·04 (Mann-Whitney U test). d) Processed RNAseq data from matched initial and recurrent disease of 28 LGG were retrieved from the GlioVis portal and V-ATPase subunit expression was examined. Significance of pairwise comparisons was obtained by Tukey's Honest Significant test. Data are presented as box plots (lower, median and upper quartile) with whiskers indicating the minimum and maximum values. e) Heatmap showing eight V-ATPase subunits in LGG/IDHwt patients (n = 76; TCGA dataset). f) ROC curve analysis coupled with the Youden's J statistic was used to identify the best classifiers for sorting LGG/IDHmut from GBM cases (training set). Simultaneous down-regulation of ATP6V1G2, ATP6V1C1, and ATP6V0A1 provided the best classification (sensitivity, 97%; specificity, 95%; see Table S11). g) LGG/IDHwt cases were annotated as LGG/IDHmut-like or GBM-like according to the ROC-generated cut-off determined in f. Principal component analysis (PCA) of V-ATPase genes in LGG/IDHwt cases from the two V-ATPase classes. h) Survival analysis of LGG/IDHwt patients according to V-ATPase class. i) Percentage of dead patients according to pathomolecular (LGG/IDHmut and GBM) and V-ATPase class (for LGG/IDHwt cases). p < 0·0001 (Chi-square test). Mean survival times were 26·7, 19·2, 13·9 and 11·1 months, respectively.