MGMT Promoter Methylation Correlates with an Overall Survival Benefit in Chinese High-Grade Glioblastoma Patients Treated with Radiotherapy and Alkylating Agent-Based Chemotherapy: A Single-Institution Study

被引:24
作者
Shen, Dong [1 ]
Liu, Tao [1 ]
Lin, Qingfen [1 ]
Lu, Xiangdong [1 ]
Wang, Qiong [1 ]
Lin, Feng [1 ]
Mao, Weidong [1 ]
机构
[1] Southeast Univ, Coll Med, Affiliated Jiangyin Hosp, Dept Oncol, Jiangyin, Peoples R China
关键词
PROTEIN EXPRESSION; PREGNANT-WOMEN; TEMOZOLOMIDE; GENE; IMMUNOHISTOCHEMISTRY; H1N1;
D O I
10.1371/journal.pone.0107558
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Promoter methylation of the O-6-methylguanine-DNA-methyltransferase (MGMT) gene has been considered a prognostic marker and has become more important in the treatment of glioblastoma. However, reports on the correlation between MGMT and clinical outcomes in Chinese glioblastoma patients are very scarce. In this study, quantitative methylation data were obtained by the pyrosequencing of tumor tissues from 128 GBM patients. The median overall survival (OS) was 13.1 months, with a 1-year survival of 45.3%. The pyrosequencing data were reproducible based on archived samples yielding data for all glioblastomas. MGMT promoter methylation was detected in 75/128 cases (58.6%), whereas 53/128 (41.4%) cases were unmethylated. Further survival analysis also revealed that methylation was an independent prognostic factor associated with prolonged OS but not with progression-free survival (PFS) (p = 0.029 and p = 0.112, respectively); the hazard radios were 0.63 (95% CI: 0.42-0.96) and 0.72 (95% CI: 0.48-1.09), respectively. These data indicated that MGMT methylation has prognostic significance in patients with newly diagnosed high-grade glioblastoma undergoing alkylating agent-based chemotherapy after surgical resection.
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页数:6
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共 29 条
[1]   MGMT methylation analysis of glioblastoma on the Infinium methylation BeadChip identifies two distinct CpG regions associated with gene silencing and outcome, yielding a prediction model for comparisons across datasets, tumor grades, and CIMP-status [J].
Bady, Pierre ;
Sciuscio, Davide ;
Diserens, Annie-Claire ;
Bloch, Jocelyne ;
van den Bent, Martin J. ;
Marosi, Christine ;
Dietrich, Pierre-Yves ;
Weller, Michael ;
Mariani, Luigi ;
Heppner, Frank L. ;
Mcdonald, David R. ;
Lacombe, Denis ;
Stupp, Roger ;
Delorenzi, Mauro ;
Hegi, Monika E. .
ACTA NEUROPATHOLOGICA, 2012, 124 (04) :547-560
[2]   Clinical neuropathology practice guide 06-2012: MGMT testing in elderly glioblastoma patients - yes, but how? [J].
Berghoff, Anna S. ;
Preusser, Matthias .
CLINICAL NEUROPATHOLOGY, 2012, 31 (06) :405-408
[3]   Relationship between Tumor Enhancement, Edema, IDH1 Mutational Status, MGMT Promoter Methylation, and Survival in Glioblastoma [J].
Carrillo, J. A. ;
Lai, A. ;
Nghiemphu, P. L. ;
Kim, H. J. ;
Phillips, H. S. ;
Kharbanda, S. ;
Moftakhar, P. ;
Lalaezari, S. ;
Yong, W. ;
Ellingson, B. M. ;
Cloughesy, T. F. ;
Pope, W. B. .
AMERICAN JOURNAL OF NEURORADIOLOGY, 2012, 33 (07) :1349-1355
[4]   Prognostic Value of Three Different Methods of MGMT Promoter Methylation Analysis in a Prospective Trial on Newly Diagnosed Glioblastoma [J].
Christians, Arne ;
Hartmann, Christian ;
Benner, Axel ;
Meyer, Jochen ;
von Deimling, Andreas ;
Weller, Michael ;
Wick, Wolfgang ;
Weiler, Markus .
PLOS ONE, 2012, 7 (03)
[5]   MGMT activity, promoter methylation and immunohistochemistry of pretreatment and recurrent malignant gliomas: a comparative study on astrocytoma and glioblastoma [J].
Christmann, Markus ;
Nagel, Georg ;
Horn, Sigrid ;
Krahn, Ulrike ;
Wiewrodt, Dorothee ;
Sommer, Clemens ;
Kaina, Bernd .
INTERNATIONAL JOURNAL OF CANCER, 2010, 127 (09) :2106-2118
[6]   Prognostic value of MGMT promoter methylation in glioblastoma patients treated with temozolomide-based chemoradiation: A Portuguese multicentre study [J].
Costa, Bruno M. ;
Caeiro, Claudia ;
Gumaraes, Ines ;
Martinho, Olga ;
Jaraquemada, Teresa ;
Augusto, Isabel ;
Castro, Ligia ;
Osorio, Ligia ;
Linhares, Paulo ;
Honavar, Mrinalini ;
Resende, Mario ;
Braga, Fatima ;
Silva, Ana ;
Pardal, Fernando ;
Amorim, Julia ;
Nabico, Rui ;
Almeida, Rui ;
Alegria, Carlos ;
Pires, Manuel ;
Pinheiro, Celia ;
Carvalho, Ernesto ;
Lopes, Jose M. ;
Costa, Paulo ;
Damasceno, Margarida ;
Reis, Rui M. .
ONCOLOGY REPORTS, 2010, 23 (06) :1655-1662
[7]   MGMT expression and promoter methylation status may depend on the site of surgical sample collection within glioblastoma: a possible pitfall in stratification of patients? [J].
Della Puppa, Alessandro ;
Persano, Luca ;
Masi, Giulia ;
Rampazzo, Elena ;
Sinigaglia, Alessandro ;
Pistollato, Francesca ;
Denaro, Luca ;
Barzon, Luisa ;
Palu, Giorgio ;
Basso, Giuseppe ;
Scienza, Renato ;
d'Avella, Domenico .
JOURNAL OF NEURO-ONCOLOGY, 2012, 106 (01) :33-41
[8]   MGMT promoter methylation correlates with survival benefit and sensitivity to temozolomide in pediatric glioblastoma [J].
Donson, Andrew M. ;
Addo-Yobo, Steven O. ;
Handler, Michael H. ;
Gore, Lia ;
Foreman, Nicholas K. .
PEDIATRIC BLOOD & CANCER, 2007, 48 (04) :403-407
[9]   An analysis of image texture, tumor location, and MGMT promoter methylation in glioblastoma using magnetic resonance imaging [J].
Drabycz, Sylvia ;
Roldan, Gloria ;
de Robles, Paula ;
Adler, Daniel ;
McIntyre, John B. ;
Magliocco, Anthony M. ;
Cairncross, J. Gregory ;
Mitchell, J. Ross .
NEUROIMAGE, 2010, 49 (02) :1398-1405
[10]   Extent of MGMT promoter methylation correlates with outcome in glioblastomas given temozolomide and radiotherapy [J].
Dunn, J. ;
Baborie, A. ;
Alam, F. ;
Joyce, K. ;
Moxham, M. ;
Sibson, R. ;
Crooks, D. ;
Husband, D. ;
Shenoy, A. ;
Brodbelt, A. ;
Wong, H. ;
Liloglou, T. ;
Haylock, B. ;
Walker, C. .
BRITISH JOURNAL OF CANCER, 2009, 101 (01) :124-131