The effects of O6-methyl guanine DNA-methyl transferase promotor methylation and CpG1, CpG2, CpG3 and CpG4 methylation on treatment response and their prognostic significance in patients with glioblastoma

Characteristics	All Patients		MGMT-Methylated		MGMT-Unmethylated
	n	%	n	%	n	%
Gender:
males	65	65.0	36	69.2	29	60.4
females	35	35.0	16	30.8	19	39.6

Age (years):
<60	67	67.0	38	73.1	29	60.4
>60	33	33.0	14	26.9	19	39.6

Tumor location:
frontal lobe	17	17.0	11	21.2	6	12.5
parietal lobe	25	25.0	13	25.0	12	25.0
temporal lobe	17	17.0	8	15.4	9	18.8
occipital lobe	3	3.0	1	1.9	2	4.2
basal ganglion	2	2.0	1	1.9	1	2.1
brain stem	2	2.0	1	1.9	1	2.1
cerebellum	5	5.0	1	1.9	4	8.3
multi-lobar	29	29.0	16	30.8	13	27.1

Number of tumors:
single	96	96.0	49	94.2	47	97.9
multiple	4	4.0	3	5.8	1	2.1

Type of surgery:
total resection	79	79.0	41	78.8	38	79.2
subtotal resection	17	17.0	7	13.5	10	20.8
biopsy	4	4.0	4	7.7	0	00.0

Treatment:
RT+TMZ	55	55.0	23	44.2	32	66.7
RT only	45	45.0	29	55.8	16	33.3

Recurrence location:
in the area	31	31.0	11	21.2	20	41.7
out of the area	37	37.0	21	40.4	16	33.3
in+out of area	14	14.0	9	17.3	5	10.4

Second series treatment	21	21.0	15	28.8	6	12.5
	2	2.0	1	1.9	1	2.1
	4	4.0	1	1.9	3	6.3
	73	73.0	24.0	67.3	38	79.2

[i] MGMT: O⁶-methyl guanine-methyl transferase; RT: radiotherapy; TMZ: temozolomide.

Table 2

Multivariate analysis according to risk factors for overall survival.

	All Patients			MGMT-Methylated			MGMT-Unmethylated
Parameters	OR	95% CI	p Value	OR	95% CI	p Value	OR	95% CI	p Value
Age	0.493	0.313-0.777	0,0002	0.524	0.267-1.031	0.05	0.485	0.256-0.920	0.02
Gender (males/females)	0.955	0.618-1.476	0.8	1.066	0.564-2.015	0.8	0.999	0.541-1.844	0.9
TMZ treatment included	0.546	0.353-0.845	0.006	0.293	0.146-0.587	<0.0001	0.930	0.496-1.745	0.8
MGMT-methylation	0.609	0.395-0.939	0.02	-	-	-	-	-	-

[i] MGMT: O⁶-methyl guanine-methyl transferase; TMZ: temozolomide.

Table 3

Multivariate analysis according to risk factors for progression-free survival.

	All Patients			MGMT-Methylated			MGMT-Unmethylated
Parameters	OR	95% CI	p Value	OR	95% CI	p Value	OR	95% CI	p Value
Age	0.809	0.521-1.254	0.3	0.872	0.451-1.687	0.6	0.952	0.516-1.756	0.8
Gender (males/females)	1.033	0.665-1.605	0.8	1.3	0.658-2.568	0.4	1.04	0.564-1.920	0.8
TMZ treatment included	0.515	0.332-0.798	0.03	0.285	0.142-0.575	<0.0001	0.90	0.472-1.714	0.7
MGMT-methylation	0.662	0.430-1.019	0.05	-	-	-	-	-	-

[i] MGMT: O⁶-methyl guanine-methyl transferase; TMZ: temozolomide.

Overall survival curve for patients with MGMT-methylation receiving RT+TMZ and RT only **(a)**. Progression free survival curve for patients with MGMT-methylation receiving RT+TMZ and RT only **(b)**. The OS curve for patients without MGMT-methylation receiving RT+TMZ and RT only **(c)**. The PFS curve for patients without MGMT-methylation receiving RT+TMZ and RT only **(d)**. The OS curve for patients with and without MGMT-methylation receiving RT+TMZ and RT only **(e)**. The PFS curve for patients with and without MGMT-methylation receiving RT+TMZ and only RT **(f)**.

The PFS curve for patients receiving RT and positive for CpG3 island methylation **(a)**. The PFS curve for patients receiving RT and positive for CpG2 island methylation **(b)**. The PFS curve for patients with CpGl island methylation and receiving RT **(c)**. The PFS curve for patients with CpG3 island methylation and receiving RT+TMZ and RT **(d)**.

Table 4

Multivariate analysis according to CpG island methylation status for overall survival.

	Methylated MGMT Patients Receiving RT+TMZ			Methylated MGMT Patients Receiving RT			Methylated MGMT Patients			All Patients
	OR	95% CI	p Value	OR	95% CI	p Value	OR	95% CI	p Value	OR	95% CI	p Value
CpG1	0.243	0.044-1.332	0.07	2.077	0.867-4972	0.09	1.552	0.701-3.437	0.2	1.552	0.701-3.437	0.2
CpG2	0.243	0.044-1.332	0.07	1.490	0.598-3.713	0.3	1.121	0.498-2.523	0.7	1.121	0.498-2.523	0.71
CpG3	0.533	0.115-2.477	0.4	1.818	0.788-4.193	0.1	1.479	0.692-3.158	0.3	1.479	0.692-3.158	0.3
CpG4	-	-	-	0.325	0.041-2.603	0.3	0.325	0.041-2.603	0.2	0.325	0.041-2.603	0.2

[i] MGMT: O⁶-methyl guanine-methyl transferase; RT: radiotherapy; TMZ: temozolomide.

Table 5

Multivariate analysis according to CpG island methylation status for progression-free survival.

	Methylated MGMT Patients Receiving RT+TMZ			Methylated MGMT Patients Receiving RT			Methylated MGMT Patients			All Patients
	OR	95% CI	p Value	OR	95% CI	p Value	OR	95% CI	p Value	OR	95% CI	p Value
CpG1	0.482	0.103-2.255	0.3	2.666	1.052-6.757	0.03	1.977	0.866-4.513	0.1	1.977	0.866-4.513	0.1
CpG2	0.482	0.103-2.255	0.3	2.838	0.958-8.404	0.05	1.931	0.779-4.791	0.1	1.931	0.779-4.791	0.1
CpG3	1.365	0.301-6.198	0.6	2.453	1.015-5.926	0.04	2.156	0.994-4.678	0.04	2.156	0.994-4.678	0.04
CpG4	-	-	-	-	-	-	1.099	0.147-8.212	0.9	1.099	0.147-8.212	0.9

[i] MGMT: O⁶-methyl guanine-methyl transferase; RT: radiotherapy; TMZ: temozolomide.

References

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Articles in this issue

DOI: https://doi.org/10.2478/bjmg-2020-0015 | Journal eISSN: 2199-5761 (formerly 1311-0160) | Journal ISSN: 1311-0160

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Language: English

Page range: 33 - 41

Published on: Aug 26, 2020

Published by: Macedonian Academy of Sciences and Arts

In partnership with: Paradigm Publishing Services

Keywords:

Glioblastoma (GB),

O⁶-Methyl guanine methyl transferase (MGMT) methylation,

Radiotherapy (RT)

Related subjects:

Medicine,

Basic medical science,

Basic medical science, other

© 2020 OG Yildiz, D Aslan, H Akalin, Y Erdem, O Canoz, A Aytekin, S Ozoner, M Dundar, published by Macedonian Academy of Sciences and Arts
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Volume 23 (2020): Issue 1 (June 2020)

The effects of O6-methyl guanine DNA-methyl transferase promotor methylation and CpG1, CpG2, CpG3 and CpG4 methylation on treatment response and their prognostic significance in patients with glioblastoma

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