The prognostic value of MGMT promoter methylation in Glioblastoma multiforme: a meta-analysis

被引：90

作者：

Zhang, Kui ^{[1
,2
]}

Wang, Xiao-qin ^{[3
]}

Zhou, Bin ^{[4
,5
]}

Zhang, Lin ^{[2
,4
,5
]}

机构：

[1] Zun Yi Med Coll, Dept Forens Med, Zun Yi 563003, Peoples R China

[2] Sichuan Univ, West China Sch Preclin & Forens Med, Dept Forens Biol, Chengdu 610041, Sichuan, Peoples R China

[3] Sichuan Univ, West China Univ Hosp 2, Dept Pediat Cardiol, Chengdu 610041, Sichuan, Peoples R China

[4] Sichuan Univ, West China Univ Hosp 2, West China Inst Women & Childrens Hlth, Lab Mol Translat Med, Chengdu 610041, Sichuan, Peoples R China

[5] Sichuan Univ, Minist Educ, Key Lab Obstet & Gynecol & Pediat Dis & Birth Def, Chengdu 610041, Sichuan, Peoples R China

来源：

FAMILIAL CANCER | 2013年 / 12卷 / 03期

关键词：

Glioblastoma multiforme; O-6-Methylguanine-DNA methyltransferase (MGMT); Methylation; Prognostic factors; Meta-analysis; NEWLY-DIAGNOSED GLIOBLASTOMA; O-6-METHYLGUANINE-DNA METHYLTRANSFERASE; O6-METHYLGUANINE-DNA METHYLTRANSFERASE; IMMUNOHISTOCHEMICAL EXPRESSION; ADJUVANT TEMOZOLOMIDE; PROTEIN EXPRESSION; MISMATCH REPAIR; GENE; RADIOTHERAPY; CONCOMITANT;

D O I：

10.1007/s10689-013-9607-1

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The prognostic significance of O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation on Glioblastoma multiforme (GBM) remains controversial. A meta-analysis of published studies investigating the effects of MGMT promoter methylation on both progression-free survival (PFS) and overall survival (OS) among GBM patients was performed. A total of 2,986 patients from 30 studies were included in the meta-analysis. In all, the frequency of MGMT promoter methylation was 44.27 %. Five studies undertook univariate analyses and nine undertook multivariate analyses of MGMT promoter methylation on PFS. The pooled hazard ratio (HR) estimate for PFS was 0.72 (95 % CI 0.55-0.95) by univariate analysis and 0.51 (95 % CI 0.38-0.69) by multivariate analysis. The effect of MGMT promoter methylation on OS was evaluated in 15 studies by univariate analysis and 14 studies by multivariate analysis. The combined HR was 0.67 (95 % CI 0.58-0.78) and 0.49 (95 % CI 0.38-0.64), respectively. For GBM patients treated with Alkylating agent, the meta-risk remained highly significant by both univariate (HR = 0.58; 95 % CI 0.42-0.79) and multivariate analysis (HR = 0.42; 95 % CI 0.29-0.60). This study showed that MGMT promoter methylation was associated with better PFS and OS in patients with GBM regardless of therapeutic intervention, and associated with longer OS in GBM patients treated with alkylating agents.

引用

页码：449 / 458

页数：10

共 57 条

[41] Repair of O6-alkylguanine by alkyltransferases [J].

Pegg, AE .

MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH, 2000, 462 (2-3) :83-100

[42] Predictive impact of MGMT promoter methylation in glioblastoma of the elderly [J].

Reifenberger, Guido ;

Hentschel, Bettina ;

Felsberg, Joerg ;

Schackert, Gabriele ;

Simon, Matthias ;

Schnell, Oliver ;

Westphal, Manfred ;

Wick, Wolfgang ;

Pietsch, Torsten ;

Loeffler, Markus ;

Weller, Michael .

INTERNATIONAL JOURNAL OF CANCER, 2012, 131 (06) :1342-1350

[43] MGMT promoter methylation is predictive of response to radiotherapy and prognostic in the absence of adjuvant alkylating chemotherapy for glioblastoma [J].

Rivera, Andreana L. ;

Pelloski, Christopher E. ;

Gilbert, Mark R. ;

Colman, Howard ;

De La Cruz, Clarissa ;

Sulman, Erik P. ;

Bekele, B. Nebiyou ;

Aldape, Kenneth D. .

NEURO-ONCOLOGY, 2010, 12 (02) :116-121

[44]

SILBER JR, 1993, CANCER RES, V53, P3416

[45] Prospective trial of gross-total resection with Gliadel wafers followed by early postoperative Gamma Knife radiosurgery and conformal fractionated radiotherapy as the initial treatment for patients with radiographically suspected, newly diagnosed glioblastoma multiforme [J].

Smith, Kris A. ;

Ashby, Lynn S. ;

Gonzalez, Fernando ;

Brachman, David G. ;

Thomas, Terry ;

Coons, Stephen W. ;

Battaglia, Matthew ;

Scheck, Adrienne C. .

JOURNAL OF NEUROSURGERY, 2008, 109 :106-117

[46] O 6-Methylguanine DNA methyltransferase determined by promoter hypermethylation and immunohistochemical expression is correlated with progression-free survival in patients with glioblastoma [J].

Sonoda, Yukihiko ;

Yokosawa, Michiko ;

Saito, Ryuta ;

Kanamori, Masayuki ;

Yamashita, Yoji ;

Kumabe, Toshihiro ;

Watanabe, Mika ;

Tominaga, Teiji .

INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY, 2010, 15 (04) :352-358

[47] Long-term survivors of glioblastoma: clinical features and molecular analysis [J].

Sonoda, Yukihiko ;

Kumabe, Toshihiro ;

Watanabe, Mika ;

Nakazato, Yoichi ;

Inoue, Tomoo ;

Kanamori, Masayuki ;

Tominaga, Teiji .

ACTA NEUROCHIRURGICA, 2009, 151 (11) :1349-1358

[48] Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma [J].

Stupp, R ;

Mason, WP ;

van den Bent, MJ ;

Weller, M ;

Fisher, B ;

Taphoorn, MJB ;

Belanger, K ;

Brandes, AA ;

Marosi, C ;

Bogdahn, U ;

Curschmann, J ;

Janzer, RC ;

Ludwin, SK ;

Gorlia, T ;

Allgeier, A ;

Lacombe, D ;

Cairncross, JG ;

Eisenhauer, E ;

Mirimanoff, RO ;

Van Den Weyngaert, D ;

Kaendler, S ;

Krauseneck, P ;

Vinolas, N ;

Villa, S ;

Wurm, RE ;

Maillot, MHB ;

Spagnolli, F ;

Kantor, G ;

Malhaire, JP ;

Renard, L ;

De Witte, O ;

Scandolaro, L ;

Vecht, CJ ;

Maingon, P ;

Lutterbach, J ;

Kobierska, A ;

Bolla, M ;

Souchon, R ;

Mitine, C ;

Tzuk-Shina, T ;

Kuten, A ;

Haferkamp, G ;

de Greve, J ;

Priou, F ;

Menten, J ;

Rutten, I ;

Clavere, P ;

Malmstrom, A ;

Jancar, B ;

Newlands, E .

NEW ENGLAND JOURNAL OF MEDICINE, 2005, 352 (10) :987-996

[49] Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial [J].

Stupp, Roger ;

Hegi, Monika E. ;

Mason, Warren P. ;

van den Bent, Martin J. ;

Taphoorn, Martin J. B. ;

Janzer, Robert C. ;

Ludwin, Samuel K. ;

Allgeier, Anouk ;

Fisher, Barbara ;

Belanger, Karl ;

Hau, Peter ;

Brandes, Alba A. ;

Gijtenbeek, Johanna ;

Marosi, Christine ;

Vecht, Charles J. ;

Mokhtari, Karima ;

Wesseling, Pieter ;

Villa, Salvador ;

Eisenhauer, Elizabeth ;

Gorlia, Thierry ;

Weller, Michael ;

Lacombe, Denis ;

Cairncross, J. Gregory ;

Mirimanoff, Rene-Olivier .

LANCET ONCOLOGY, 2009, 10 (05) :459-466

[50] Clinical correlation of MGMT protein expression and promoter methylation in Chinese glioblastoma patients [J].

Tang, Kai ;

Jin, Qiang ;

Yan, Wei ;

Zhang, Wei ;

You, Gan ;

Liu, Yanwei ;

Jiang, Tao .

MEDICAL ONCOLOGY, 2012, 29 (02) :1292-1296

← 1 2 3 4 5 6 →