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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

OG Yildiz
OG Yildiz
, 
D Aslan
D Aslan
, 
H Akalin
H Akalin
, 
Y Erdem
Y Erdem
, 
O Canoz
O Canoz
, 
A Aytekin
A Aytekin
, 
S Ozoner
S Ozoner
 oraz 
M Dundar
M Dundar
   | 26 sie 2020
Balkan Journal of Medical Genetics's Cover Image
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Article Category: Original Article
Data publikacji: 26 sie 2020
Zakres stron: 33 - 41
DOI: https://doi.org/10.2478/bjmg-2020-0015
Słowa kluczowe
© 2020 Yildiz OG, Aslan D, Akalin H, Erdem Y, Canoz O, Aytekin A, Ozoner S, Dundar M, published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Figure 1

A positive case for MGMT-methylation (in the CpG1 island there was 40.0%, in the CpG2 island 36.0%, in the CpG3 island 47.0% and in the CpG4 island 59.0% positivity was detected) (a). A positive case positive for MGMT-methylation (in the CpG2 island there was 60.0% positivity) (b). A case with negative MGMT-methylation (in the CpG1 island there was 3.0%, in the CpG2 island 2.0%, in the CpG3 island 4.0% and in the CpG4 island 4.0% positivity was detected) (c).
A positive case for MGMT-methylation (in the CpG1 island there was 40.0%, in the CpG2 island 36.0%, in the CpG3 island 47.0% and in the CpG4 island 59.0% positivity was detected) (a). A positive case positive for MGMT-methylation (in the CpG2 island there was 60.0% positivity) (b). A case with negative MGMT-methylation (in the CpG1 island there was 3.0%, in the CpG2 island 2.0%, in the CpG3 island 4.0% and in the CpG4 island 4.0% positivity was detected) (c).

Figure 2

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).
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).

Figure 3

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).
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).

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

All PatientsMGMT-MethylatedMGMT-Unmethylated
ParametersOR95% CIp ValueOR95% CIp ValueOR95% CIp Value
Age0.8090.521-1.2540.30.8720.451-1.6870.60.9520.516-1.7560.8
Gender (males/females)1.0330.665-1.6050.81.30.658-2.5680.41.040.564-1.9200.8
TMZ treatment included0.5150.332-0.7980.030.2850.142-0.575<0.00010.900.472-1.7140.7
MGMT-methylation0.6620.430-1.0190.05------

Multivariate analysis according to risk factors for overall survival.

All PatientsMGMT-MethylatedMGMT-Unmethylated
ParametersOR95% CIp ValueOR95% CIp ValueOR95% CIp Value
Age0.4930.313-0.7770,00020.5240.267-1.0310.050.4850.256-0.9200.02
Gender (males/females)0.9550.618-1.4760.81.0660.564-2.0150.80.9990.541-1.8440.9
TMZ treatment included0.5460.353-0.8450.0060.2930.146-0.587<0.00010.9300.496-1.7450.8
MGMT-methylation0.6090.395-0.9390.02------

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

Methylated MGMT Patients Receiving RT+TMZMethylated MGMT Patients Receiving RTMethylated MGMT PatientsAll Patients
OR95% CIp ValueOR95% CIp ValueOR95% CIp ValueOR95% CIp Value
CpG10.2430.044-1.3320.072.0770.867-49720.091.5520.701-3.4370.21.5520.701-3.4370.2
CpG20.2430.044-1.3320.071.4900.598-3.7130.31.1210.498-2.5230.71.1210.498-2.5230.71
CpG30.5330.115-2.4770.41.8180.788-4.1930.11.4790.692-3.1580.31.4790.692-3.1580.3
CpG4---0.3250.041-2.6030.30.3250.041-2.6030.20.3250.041-2.6030.2

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

Methylated MGMT Patients Receiving RT+TMZMethylated MGMT Patients Receiving RTMethylated MGMT PatientsAll Patients
OR95% CIp ValueOR95% CIp ValueOR95% CIp ValueOR95% CIp Value
CpG10.4820.103-2.2550.32.6661.052-6.7570.031.9770.866-4.5130.11.9770.866-4.5130.1
CpG20.4820.103-2.2550.32.8380.958-8.4040.051.9310.779-4.7910.11.9310.779-4.7910.1
CpG31.3650.301-6.1980.62.4531.015-5.9260.042.1560.994-4.6780.042.1560.994-4.6780.04
CpG4------1.0990.147-8.2120.91.0990.147-8.2120.9

Patient characteristics.

CharacteristicsAll PatientsMGMT-MethylatedMGMT-Unmethylated
n%n%n%
Gender:
    males6565.03669.22960.4
    females3535.01630.81939.6
Age (years):
    <606767.03873.12960.4
    >603333.01426.91939.6
Tumor location:
    frontal lobe1717.01121.2612.5
    parietal lobe2525.01325.01225.0
    temporal lobe1717.0815.4918.8
    occipital lobe33.011.924.2
    basal ganglion22.011.912.1
    brain stem22.011.912.1
    cerebellum55.011.948.3
    multi-lobar2929.01630.81327.1
Number of tumors:
    single9696.04994.24797.9
    multiple44.035.812.1
Type of surgery:
    total resection7979.04178.83879.2
    subtotal resection1717.0713.51020.8
    biopsy44.047.7000.0
Treatment:
    RT+TMZ5555.02344.23266.7
    RT only4545.02955.81633.3
Recurrence location:
    in the area3131.01121.22041.7
    out of the area3737.02140.41633.3
    in+out of area1414.0917.3510.4
Second series treatment2121.01528.8612.5
22.011.912.1
44.011.936.3
7373.024.067.33879.2
eISSN:
1311-0160
Język:
Angielski
Częstotliwość wydawania:
2 razy w roku
Dziedziny czasopisma:
Medicine, Basic Medical Science, other
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