DNA methylation-based age acceleration observed in IDH wild-type glioblastoma is associated with better outcome—including in elderly patients

Table 3 Multivariable Cox regression models including age acceleration, GBM classification, global HM-entropy (HME) and HME at promoter CpGs

Model	Variables	EORTC/NCIC & LN-Pilot (N = 177)				Nordic study (N = 105)
Model	Variables	Modality	HR	z-value	Pr( >\|z\|)	Modality	HR	z-value	Pr( >\|z\|)
Age acceleration [years]
	Treatment (TRT)	TMZ + RT	1.34862	1.31435	0.18873	TMZ	1.06845	0.23966	0.81059
	MGMT	MGMTmeth	0.77273	− 1.10615	0.26866	MGMTmeth	1.13894	0.50912	0.61067
	Age Acceleration		0.99124	− 2.46259	0.01379		0.98549	− 3.15493	0.00161
	TRT x MGMT	TMZ + RT x MGMTmeth	0.27215	− 3.94628	0.00008	TMZ x MGMTmeth	0.47267	− 1.66716	0.09548
GBM classification
	Treatment (TRT)	TMZ + RT	1.19859	0.80597	0.42026	TMZ	1.12226	0.41692	0.67674
	MGMT	MGMTmeth	0.70503	− 1.52048	0.12839	MGMTmeth	1.05817	0.22379	0.82292
	GBM classification	GBM_RTK_I	1.54086	1.91764	0.05516	GBM_RTK_I	1.12308	0.41675	0.67686
		GBM_RTK_II	0.91674	− 0.48386	0.62848	GBM_RTK_II	0.52912	− 2.63579	0.00839
	TRT x MGMT	TMZ + RT x MGMTmeth	0.31994	− 3.55697	0.00038	TMZ x MGMTmeth	0.53507	− 1.39736	0.16230
Global HME
	Treatment (TRT)	TMZ + RT	1.12690	0.55400	0.57958	TMZ	1.08996	0.30807	0.75803
	MGMT	MGMTmeth	0.69179	− 1.61442	0.10644	MGMTmeth	0.89983	− 0.42203	0.67300
	HME		3.18126	0.49623	0.61973		164.80788	1.64897	0.09915
		TMZ + RT x MGMTmeth	0.34584	− 3.38245	0.00072	TMZ x MGMTmeth	0.54313	− 1.36378	0.17264
HME promoter CpG
	Treatment (TRT)	TMZ + RT	1.15106	0.65024	0.51554	TMZ	1.17499	0.58063	0.56149
	MGMT	Methylated	0.73235	− 1.33193	0.18288	MGMTmeth	0.95937	− 0.16478	0.86912
	HME prom CpG		0.04405	− 1.14097	0.25388		0.16488	− 0.58312	0.55982
	TRT x MGMT	TMZ + RT x MGMTmeth	0.33173	− 3.48833	0.00049	TMZ x MGMTmeth	0.53779	− 1.39207	0.16390

Cox models, adjusted for Treatment (TRT), methylation status of MGMT promoter (MGMT), and the interaction of these two variables (TRT X MGMT)
HME, human methylation entropy; HR, hazard ratio; MGMTmeth, methylated MGMT; Pr(( >|z|), p-value for z-statistics; P-value <0.5, bold

ISSN: 2051-5960