Transcriptional Characterization of Glioma Neural Stem Cells Diva ...

7.4 Survival Analysis Results
Table 7.6: Significance of survival association for GNS signature and IDH1 status.
dataset Number
of cases
Single covariate Two covariates (GBM cases)
GNS signature IDH1 status GNS signature IDH1 status
TCGA 270 5.3x10-5 0.0015 0.0091 0.1489
Gravendeel,
GBM cases
118 2.7x10-5 0.0031 9.2x10-4 0.0840
Gravendeel
et al, grade
I-III cases
86 6.5x10-4 0.5776 6.3x-4 0.5408
Wald test p-values, indicating association with survival, for each covariate in a Cox
proportional hazards model with one or two covariates (GNS signature, IDH1 status
or both). Cases with unknown IDH1 mutation status were excluded.
signature scores than IDH1 wild-type gliomas of the same histological grade
(Fig 7.6b). However, we also found that the GNS signature bore a stronger
survival association than the IDH1 status (Table 7.6). In fact, the signature
remained a significant predictor of patient survival when controlling for IDH1
status (Table 7.6), demonstrating that it contributes independent information
to the survival model and does not simply represent a transcriptional state of
IDH1 wild-type tumours. This was evident in glioblastomas as well as grade
I-III gliomas; the effect is thus not limited to grade IV tumours.
Finally, to investigate whether the correlation between GNS signature and
age could be explained by the higher proportion of cases with IDH1 mutation
among younger patients, we repeated the correlation analysis described above
(Fig 7.6a), limiting the data to glioblastoma cases without IDH1 mutation. For
the TCGA dataset, the correlation was decreased somewhat (Pearson R = 0.25
compared to R = 0.36 for the full dataset) but still highly significant (p =
6x10 5 ), demonstrating that the correlation with age is only partially explained
by IDH1 status. This result was confirmed in the Gravendeel dataset, where
the effect of controlling for IDH1 status and grade was negligible (R = 0.38
compared to R = 0.39 for the full dataset including grade I-III samples).
Among the individual signature genes, both HOXD10 and TUSC3 remained
correlated with age in both datasets when limiting the analysis to IDH1 wild-
type glioblastoma cases.
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