Advertisement

Neurochemical Research

, Volume 39, Issue 12, pp 2277–2287 | Cite as

The Prognosis of MGMT Promoter Methylation in Glioblastoma Patients of Different Race: A Meta-analysis

  • Haiyu Yang
  • Danping Wei
  • Kunxian Yang
  • Wenru Tang
  • Ying Luo
  • Jihong Zhang
Overview

Abstract

O6-Methylguanine-DNA methyltransferase (MGMT) is a DNA repair gene. Epigenetic silencing of the MGMT promoter methylation compromises DNA repair and has been associated with longer survival in patients with glioblastoma (GBM) who receive alkylating agents. But the prognostic of MGMT promoter methylation in GBM patients of different race is still ambiguous. Based on an univariate or multivariate analysis between different race (Caucasian and Asian), a meta-analysis of the effects of MGMT promoter methylation on both progression-free survival (PFS) and overall survival (OS) among GBM patients was conducted. A total of 6,309 patients from 50 studies were involved in the analysis. Random effect models were applied to estimate the pooled hazard ratio (HR) with 95 % confidence intervals (CIs) for GBM patients of different race prognosis, the Chi square-based Q test was used to test heterogeneity. Begg’s (funnel plot method) and Egger’s linear regression tests were adopted to check publication bias (a bias with regard to what is likely to be published, among what is available to be published). The HR value estimated for OS was 0.524 (95 % CI 0.428–0.640) by univariate analysis and 0.427 (95 % CI 0.355–0.513) by multivariate analysis in Caucasian. The HR value estimated for OS was 0.892 (95 % CI 0.469–1.698) by univariate analysis and 0.562 (95 % CI 0.394–0.804) by multivariate analysis in Asian. The HR value estimated for PFS was 0.526 (95 % CI 0.372–0.743) by univariate analysis and 0.437 (95 % CI 0.356–0.537) by multivariate analysis in Caucasian. The HR value estimated for PFS was 0.132 (95 % CI 0.006–3.027) by multivariate analysis in Asian. This data revealed that GBM patients with MGMT promoter methylation had longer OS and PFS by univariate or multivariate analysis in Caucasian regardless of therapeutic intervention. However, GBM patients with MGMT promoter methylation only had longer OS by multivariate analysis in Asian.

Keywords

Meta-analysis Glioblastoma Promoter methylation Prognostic factors O6-Methylguanine-DNA methyltransferase (MGMT

Notes

Acknowledgements

This work was financially supported by the National Science Foundation of China (No.81260501, U1202221, U1132604).

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Dolecek TA, Propp JM, Stroup NE, Kruchko C (2012) CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2005–2009. Neuro-oncology 14(Suppl 5):v1–v49. doi: 10.1093/neuonc/nos218 PubMedCentralPubMedCrossRefGoogle Scholar
  2. 2.
    Yin AA, Zhang LH, Cheng JX, Dong Y, Liu BL, Han N, Zhang X (2014) The predictive but not prognostic value of MGMT promoter methylation status in elderly glioblastoma patients: a meta-analysis. PLoS ONE 9(1):e85102. doi: 10.1371/journal.pone.0085102 PubMedCentralPubMedCrossRefGoogle Scholar
  3. 3.
    Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, 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 (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352(10):987–996. doi: 10.1056/NEJMoa043330 PubMedCrossRefGoogle Scholar
  4. 4.
    Sharma S, Salehi F, Scheithauer BW, Rotondo F, Syro LV, Kovacs K (2009) Role of MGMT in tumor development, progression, diagnosis, treatment and prognosis. Anticancer Res 29(10):3759–3768PubMedGoogle Scholar
  5. 5.
    Vlassenbroeck I, Califice S, Diserens AC, Migliavacca E, Straub J, Di Stefano I, Moreau F, Hamou MF, Renard I, Delorenzi M, Flamion B, DiGuiseppi J, Bierau K, Hegi ME (2008) Validation of real-time methylation-specific PCR to determine O6-methylguanine-DNA methyltransferase gene promoter methylation in glioma. J Mol Diagn 10(4):332–337. doi: 10.2353/jmoldx.2008.070169 PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Vlachostergios PJ, Hatzidaki E, Befani CD, Liakos P, Papandreou CN (2013) Bortezomib overcomes MGMT-related resistance of glioblastoma cell lines to temozolomide in a schedule-dependent manner. Invest New Drugs 31(5):1169–1181. doi: 10.1007/s10637-013-9968-1 PubMedCrossRefGoogle Scholar
  7. 7.
    Qiu ZK, Shen D, Chen YS, Yang QY, Guo CC, Feng BH, Chen ZP (2014) Enhanced MGMT expression contributes to temozolomide resistance in glioma stem-like cells. Chin J Cancer 33(2):115–122. doi: 10.5732/cjc.012.10236 PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Jiang X, Reardon DA, Desjardins A, Vredenburgh JJ, Quinn JA, Austin AD, Herndon JE 2nd, McLendon RE, Friedman HS (2013) O6-methylguanine-DNA methyltransferase (MGMT) immunohistochemistry as a predictor of resistance to temozolomide in primary CNS lymphoma. J Neurooncol 114(1):135–140. doi: 10.1007/s11060-013-1162-y PubMedCrossRefGoogle Scholar
  9. 9.
    Hegi ME, Liu L, Herman JG, Stupp R, Wick W, Weller M, Mehta MP, Gilbert MR (2008) Correlation of O6-methylguanine methyltransferase (MGMT) promoter methylation with clinical outcomes in glioblastoma and clinical strategies to modulate MGMT activity. J Clin Oncol 26(25):4189–4199. doi: 10.1200/jco.2007.11.5964 PubMedCrossRefGoogle Scholar
  10. 10.
    Eoli M, Menghi F, Bruzzone MG, De Simone T, Valletta L, Pollo B, Bissola L, Silvani A, Bianchessi D, D’Incerti L, Filippini G, Broggi G, Boiardi A, Finocchiaro G (2007) Methylation of O6-methylguanine DNA methyltransferase and loss of heterozygosity on 19q and/or 17p are overlapping features of secondary glioblastomas with prolonged survival. Clin Cancer Res 13(9):2606–2613. doi: 10.1158/1078-0432.ccr-06-2184 PubMedCrossRefGoogle Scholar
  11. 11.
    Chinot OL, Barrie M, Fuentes S, Eudes N, Lancelot S, Metellus P, Muracciole X, Braguer D, Ouafik L, Martin PM, Dufour H, Figarella-Branger D (2007) Correlation between O6-methylguanine-DNA methyltransferase and survival in inoperable newly diagnosed glioblastoma patients treated with neoadjuvant temozolomide. J Clin Oncol 25(12):1470–1475. doi: 10.1200/jco.2006.07.4807 PubMedCrossRefGoogle Scholar
  12. 12.
    Fiano V, Trevisan M, Trevisan E, Senetta R, Castiglione A, Sacerdote C, Gillio-Tos A, De Marco L, Grasso C, Magistrello M, Tondat F, Ruda R, Cassoni P, Soffietti R, Merletti F (2014) MGMT promoter methylation in plasma of glioma patients receiving temozolomide. J Neurooncol. doi: 10.1007/s11060-014-1395-4 PubMedGoogle Scholar
  13. 13.
    Wick W, Platten M, Weller M (2009) New (alternative) temozolomide regimens for the treatment of glioma. Neuro-oncology 11(1):69–79. doi: 10.1215/15228517-2008-078 PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, Moher D, Becker BJ, Sipe TA, Thacker SB (2000) Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA 283(15):2008–2012PubMedCrossRefGoogle Scholar
  15. 15.
    Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP, Clarke M, Devereaux PJ, Kleijnen J, Moher D (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ 339:b2700. doi: 10.1136/bmj.b2700 PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    McDonald KL, Rapkins RW, Olivier J, Zhao L, Nozue K, Lu D, Tiwari S, Kuroiwa-Trzmielina J, Brewer J, Wheeler HR, Hitchins MP (2013) The T genotype of the MGMT C>T (rs16906252) enhancer single-nucleotide polymorphism (SNP) is associated with promoter methylation and longer survival in glioblastoma patients. Eur J Cancer 49(2):360–368. doi: 10.1016/j.ejca.2012.08.012 PubMedCrossRefGoogle Scholar
  17. 17.
    Chen C, Huang R, MacLean A, Muzikansky A, Mukundan S, Wen PY, Norden AD (2013) Recurrent high-grade glioma treated with bevacizumab: prognostic value of MGMT methylation, EGFR status and pretreatment MRI in determining response and survival. J Neurooncol 115(2):267–276. doi: 10.1007/s11060-013-1225-0 PubMedCrossRefGoogle Scholar
  18. 18.
    Ellingson BM, Cloughesy TF, Pope WB, Zaw TM, Phillips H, Lalezari S, Nghiemphu PL, Ibrahim H, Naeini KM, Harris RJ, Lai A (2012) Anatomic localization of O6-methylguanine DNA methyltransferase (MGMT) promoter methylated and unmethylated tumors: a radiographic study in 358 de novo human glioblastomas. NeuroImage 59(2):908–916. doi: 10.1016/j.neuroimage.2011.09.076 PubMedCrossRefGoogle Scholar
  19. 19.
    Zunarelli E, Bigiani N, Sartori G, Migaldi M, Sgambato A, Maiorana A (2011) INI1 immunohistochemical expression in glioblastoma: correlation with MGMT gene promoter methylation status and patient survival. Pathology 43(1):17–23. doi: 10.1097/PAT.0b013e328340bb26 PubMedCrossRefGoogle Scholar
  20. 20.
    Lakomy R, Sana J, Hankeova S, Fadrus P, Kren L, Lzicarova E, Svoboda M, Dolezelova H, Smrcka M, Vyzula R, Michalek J, Hajduch M, Slaby O (2011) MiR-195, miR-196b, miR-181c, miR-21 expression levels and O-6-methylguanine-DNA methyltransferase methylation status are associated with clinical outcome in glioblastoma patients. Cancer Sci 102(12):2186–2190. doi: 10.1111/j.1349-7006.2011.02092.x PubMedCrossRefGoogle Scholar
  21. 21.
    Combs SE, Rieken S, Wick W, Abdollahi A, von Deimling A, Debus J, Hartmann C (2011) Prognostic significance of IDH-1 and MGMT in patients with glioblastoma: one step forward, and one step back? Radiat Oncol 6:115. doi: 10.1186/1748-717X-6-115 PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Thon N, Eigenbrod S, Grasbon-Frodl EM, Lutz J, Kreth S, Popperl G, Belka C, Kretzschmar HA, Tonn JC, Kreth FW (2011) Predominant influence of MGMT methylation in non-resectable glioblastoma after radiotherapy plus temozolomide. J Neurol Neurosurg Psychiatry 82(4):441–446. doi: 10.1136/jnnp.2010.214593 PubMedCrossRefGoogle Scholar
  23. 23.
    Rivera AL, Pelloski CE, Gilbert MR, Colman H, De La Cruz C, Sulman EP, Bekele BN, Aldape KD (2010) MGMT promoter methylation is predictive of response to radiotherapy and prognostic in the absence of adjuvant alkylating chemotherapy for glioblastoma. Neuro-oncology 12(2):116–121. doi: 10.1093/neuonc/nop020 PubMedCentralPubMedCrossRefGoogle Scholar
  24. 24.
    Morandi L, Franceschi E, de Biase D, Marucci G, Tosoni A, Ermani M, Pession A, Tallini G, Brandes A (2010) Promoter methylation analysis of O6-methylguanine-DNA methyltransferase in glioblastoma: detection by locked nucleic acid based quantitative PCR using an imprinted gene (SNURF) as a reference. BMC Cancer 10:48. doi: 10.1186/1471-2407-10-48 PubMedCentralPubMedCrossRefGoogle Scholar
  25. 25.
    Karayan-Tapon L, Quillien V, Guilhot J, Wager M, Fromont G, Saikali S, Etcheverry A, Hamlat A, Loussouarn D, Campion L, Campone M, Vallette FM, Gratas-Rabbia-Re C (2010) Prognostic value of O6-methylguanine-DNA methyltransferase status in glioblastoma patients, assessed by five different methods. J Neurooncol 97(3):311–322. doi: 10.1007/s11060-009-0031-1 PubMedCrossRefGoogle Scholar
  26. 26.
    Etcheverry A, Aubry M, de Tayrac M, Vauleon E, Boniface R, Guenot F, Saikali S, Hamlat A, Riffaud L, Menei P, Quillien V, Mosser J (2010) DNA methylation in glioblastoma: impact on gene expression and clinical outcome. BMC Genom 11:701. doi: 10.1186/1471-2164-11-701 CrossRefGoogle Scholar
  27. 27.
    Costa BM, Caeiro C, Guimaraes I, Martinho O, Jaraquemada T, Augusto I, Castro L, Osorio L, Linhares P, Honavar M, Resende M, Braga F, Silva A, Pardal F, Amorim J, Nabico R, Almeida R, Alegria C, Pires M, Pinheiro C, Carvalho E, Lopes JM, Costa P, Damasceno M, Reis RM (2010) Prognostic value of MGMT promoter methylation in glioblastoma patients treated with temozolomide-based chemoradiation: a Portuguese multicentre study. Oncol Rep 23(6):1655–1662PubMedGoogle Scholar
  28. 28.
    Wemmert S, Bettscheider M, Alt S, Ketter R, Kammers K, Feiden W, Steudel WI, Rahnenfuhrer J, Urbschat S (2009) p15 promoter methylation—a novel prognostic marker in glioblastoma patients. Int J Oncol 34(6):1743–1748PubMedGoogle Scholar
  29. 29.
    Prados MD, Chang SM, Butowski N, DeBoer R, Parvataneni R, Carliner H, Kabuubi P, Ayers-Ringler J, Rabbitt J, Page M, Fedoroff A, Sneed PK, Berger MS, McDermott MW, Parsa AT, Vandenberg S, James CD, Lamborn KR, Stokoe D, Haas-Kogan DA (2009) Phase II study of erlotinib plus temozolomide during and after radiation therapy in patients with newly diagnosed glioblastoma multiforme or gliosarcoma. J Clin Oncol 27(4):579–584. doi: 10.1200/jco.2008.18.9639 PubMedCentralPubMedCrossRefGoogle Scholar
  30. 30.
    Glas M, Happold C, Rieger J, Wiewrodt D, Bahr O, Steinbach JP, Wick W, Kortmann RD, Reifenberger G, Weller M, Herrlinger U (2009) Long-term survival of patients with glioblastoma treated with radiotherapy and lomustine plus temozolomide. J Clin Oncol 27(8):1257–1261. doi: 10.1200/jco.2008.19.2195 PubMedCrossRefGoogle Scholar
  31. 31.
    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 (2009) Extent of MGMT promoter methylation correlates with outcome in glioblastomas given temozolomide and radiotherapy. Br J Cancer 101(1):124–131. doi: 10.1038/sj.bjc.6605127 PubMedCentralPubMedCrossRefGoogle Scholar
  32. 32.
    Brandes AA, Franceschi E, Tosoni A, Benevento F, Scopece L, Mazzocchi V, Bacci A, Agati R, Calbucci F, Ermani M (2009) Temozolomide concomitant and adjuvant to radiotherapy in elderly patients with glioblastoma: correlation with MGMT promoter methylation status. Cancer 115(15):3512–3518. doi: 10.1002/cncr.24406 PubMedCrossRefGoogle Scholar
  33. 33.
    Smith KA, Ashby LS, Gonzalez LF, Brachman DG, Thomas T, Coons SW, Battaglia M, Scheck A (2008) 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 Neurosurg 109(Suppl):106–117. doi: 10.3171/JNS/2008/109/12/S17 PubMedGoogle Scholar
  34. 34.
    Murat A, Migliavacca E, Gorlia T, Lambiv WL, Shay T, Hamou MF, de Tribolet N, Regli L, Wick W, Kouwenhoven MC, Hainfellner JA, Heppner FL, Dietrich PY, Zimmer Y, Cairncross JG, Janzer RC, Domany E, Delorenzi M, Stupp R, Hegi ME (2008) Stem cell-related “self-renewal” signature and high epidermal growth factor receptor expression associated with resistance to concomitant chemoradiotherapy in glioblastoma. J Clin Oncol 26(18):3015–3024. doi: 10.1200/jco.2007.15.7164 PubMedCrossRefGoogle Scholar
  35. 35.
    Brell M, Tortosa A, Verger E, Gil JM, Vinolas N, Villa S, Acebes JJ, Caral L, Pujol T, Ferrer I, Ribalta T, Graus F (2005) Prognostic significance of O6-methylguanine-DNA methyltransferase determined by promoter hypermethylation and immunohistochemical expression in anaplastic gliomas. Clin Cancer Res 11(14):5167–5174. doi: 10.1158/1078-0432.CCR-05-0230 PubMedCrossRefGoogle Scholar
  36. 36.
    Yang S-H, Lee K, Yang H, Jeon B, Lee Y, Nam S, Chung D-S, Lee S, Hong Y-K (2012) O6-methylguanine-DNA-methyltransferase promoter methylation assessment by microdissection-assisted methylation-specific PCR and high resolution melting analysis in patients with glioblastomas. J Neurooncol 106(2):243–250. doi: 10.1007/s11060-011-0668-4 PubMedCrossRefGoogle Scholar
  37. 37.
    Park CK, Kim J, Yim SY, Lee AR, Han JH, Kim CY, Park SH, Kim TM, Lee SH, Choi SH, Kim SK, Kim DG, Jung HW (2011) Usefulness of MS-MLPA for detection of MGMT promoter methylation in the evaluation of pseudoprogression in glioblastoma patients. Neuro-oncology 13(2):195–202. doi: 10.1093/neuonc/noq162 PubMedCentralPubMedCrossRefGoogle Scholar
  38. 38.
    Christians A, Hartmann C, Benner A, Meyer J, von Deimling A, Weller M, Wick W, Weiler M (2012) Prognostic value of three different methods of MGMT promoter methylation analysis in a prospective trial on newly diagnosed glioblastoma. PLoS ONE 7(3):e33449. doi: 10.1371/journal.pone.0033449 PubMedCentralPubMedCrossRefGoogle Scholar
  39. 39.
    Ochsenbein AF, Schubert AD, Vassella E, Mariani L (2011) Quantitative analysis of O6-methylguanine DNA methyltransferase (MGMT) promoter methylation in patients with low-grade gliomas. J Neurooncol 103(2):343–351. doi: 10.1007/s11060-010-0395-2 PubMedCrossRefGoogle Scholar
  40. 40.
    Brandes AA, Franceschi E, Tosoni A, Bartolini S, Bacci A, Agati R, Ghimenton C, Turazzi S, Talacchi A, Skrap M, Marucci G, Volpin L, Morandi L, Pizzolitto S, Gardiman M, Andreoli A, Calbucci F, Ermani M (2010) O(6)-methylguanine DNA-methyltransferase methylation status can change between first surgery for newly diagnosed glioblastoma and second surgery for recurrence: clinical implications. Neuro-oncology 12(3):283–288. doi: 10.1093/neuonc/nop050 PubMedCentralPubMedCrossRefGoogle Scholar
  41. 41.
    Abhinav K, Aquilina K, Gbejuade H, La M, Hopkins K, Iyer V (2013) A pilot study of glioblastoma multiforme in elderly patients: treatments, O-6-methylguanine-DNA methyltransferase (MGMT) methylation status and survival. Clin Neurol Neurosurg 115(8):1375–1378. doi: 10.1016/j.clineuro.2012.12.023 PubMedCrossRefGoogle Scholar
  42. 42.
    Reifenberger G, Hentschel B, Felsberg J, Schackert G, Simon M, Schnell O, Westphal M, Wick W, Pietsch T, Loeffler M, Weller M (2012) Predictive impact of MGMT promoter methylation in glioblastoma of the elderly. Int J Cancer 131(6):1342–1350. doi: 10.1002/ijc.27385 PubMedCrossRefGoogle Scholar
  43. 43.
    Skiriute D, Vaitkiene P, Saferis V, Asmoniene V, Skauminas K, Deltuva VP, Tamasauskas A (2012) MGMT, GATA6, CD81, DR4, and CASP8 gene promoter methylation in glioblastoma. BMC Cancer 12:218. doi: 10.1186/1471-2407-12-218 PubMedCentralPubMedCrossRefGoogle Scholar
  44. 44.
    Lechapt-Zalcman E, Levallet G, Dugué AE, Vital A, Diebold M-D, Menei P, Colin P, Peruzzy P, Emery E, Bernaudin M, Chapon F, Guillamo J-S (2012) O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation and low MGMT-encoded protein expression as prognostic markers in glioblastoma patients treated with biodegradable carmustine wafer implants after initial surgery followed by radiotherapy with concomitant and adjuvant temozolomideGoogle Scholar
  45. 45.
    Carrillo JA, Lai A, Nghiemphu PL, Kim HJ, Phillips HS, Kharbanda S, Moftakhar P, Lalaezari S, Yong W, Ellingson BM, Cloughesy TF, Pope WB (2012) Relationship between tumor enhancement, edema, IDH1 mutational status, MGMT promoter methylation, and survival in glioblastoma. Am J Neuroradiol 33(7):1349–1355. doi: 10.3174/ajnr.A2950 PubMedCrossRefGoogle Scholar
  46. 46.
    Minniti G, Salvati M, Arcella A, Buttarelli F, D’Elia A, Lanzetta G, Esposito V, Scarpino S, Maurizi Enrici R, Giangaspero F (2011) Correlation between O6-methylguanine-DNA methyltransferase and survival in elderly patients with glioblastoma treated with radiotherapy plus concomitant and adjuvant temozolomide. J Neurooncol 102(2):311–316. doi: 10.1007/s11060-010-0324-4 PubMedCrossRefGoogle Scholar
  47. 47.
    Felsberg J, Thon N, Eigenbrod S, Hentschel B, Sabel MC, Westphal M, Schackert G, Kreth FW, Pietsch T, Loffler M, Weller M, Reifenberger G, Tonn JC (2011) Promoter methylation and expression of MGMT and the DNA mismatch repair genes MLH1, MSH2, MSH6 and PMS2 in paired primary and recurrent glioblastomas. Int J Cancer 129(3):659–670. doi: 10.1002/ijc.26083 PubMedCrossRefGoogle Scholar
  48. 48.
    Balana C, Carrato C, Ramirez JL, Cardona AF, Berdiel M, Sanchez JJ, Taron M, Hostalot C, Musulen E, Ariza A, Rosell R (2011) Tumour and serum MGMT promoter methylation and protein expression in glioblastoma patients. Clin Transl Oncol 13(9):677–685. doi: 10.1007/s12094-011-0714-x PubMedCrossRefGoogle Scholar
  49. 49.
    Zawlik I, Vaccarella S, Kita D, Mittelbronn M, Franceschi S, Ohgaki H (2009) Promoter methylation and polymorphisms of the MGMT gene in glioblastomas: a population-based study. Neuroepidemiology 32(1):21–29. doi: 10.1159/000170088 PubMedCrossRefGoogle Scholar
  50. 50.
    Wick W, Hartmann C, Engel C, Stoffels M, Felsberg J, Stockhammer F, Sabel MC, Koeppen S, Ketter R, Meyermann R, Rapp M, Meisner C, Kortmann RD, Pietsch T, Wiestler OD, Ernemann U, Bamberg M, Reifenberger G, von Deimling A, Weller M (2009) NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with procarbazine, lomustine, and vincristine or temozolomide. J Clin Oncol 27(35):5874–5880. doi: 10.1200/jco.2009.23.6497 PubMedCrossRefGoogle Scholar
  51. 51.
    Weller M, Felsberg J, Hartmann C, Berger H, Steinbach JP, Schramm J, Westphal M, Schackert G, Simon M, Tonn JC, Heese O, Krex D, Nikkhah G, Pietsch T, Wiestler O, Reifenberger G, von Deimling A, Loeffler M (2009) Molecular predictors of progression-free and overall survival in patients with newly diagnosed glioblastoma: a prospective translational study of the German glioma network. J Clin Oncol 27(34):5743–5750. doi: 10.1200/jco.2009.23.0805 PubMedCrossRefGoogle Scholar
  52. 52.
    Metellus P, Coulibaly B, Nanni I, Fina F, Eudes N, Giorgi R, Barrie M, Chinot O, Fuentes S, Dufour H, Ouafik L, Figarella-Branger D (2009) Prognostic impact of O6-methylguanine-DNA methyltransferase silencing in patients with recurrent glioblastoma multiforme who undergo surgery and carmustine wafer implantation: a prospective patient cohort. Cancer 115(20):4783–4794. doi: 10.1002/cncr.24546 PubMedCrossRefGoogle Scholar
  53. 53.
    van den Bent MJ, Dubbink HJ, Sanson M, van der Lee-Haarloo CR, Hegi M, Jeuken JW, Ibdaih A, Brandes AA, Taphoorn MJ, Frenay M, Lacombe D, Gorlia T, Dinjens WN, Kros JM (2009) MGMT promoter methylation is prognostic but not predictive for outcome to adjuvant PCV chemotherapy in anaplastic oligodendroglial tumors: a report from EORTC Brain Tumor Group Study 26951. J Clin Oncol 27(35):5881–5886. doi: 10.1200/jco.2009.24.1034 PubMedCentralPubMedCrossRefGoogle Scholar
  54. 54.
    Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, Ludwin SK, Allgeier A, Fisher B, Belanger K, Hau P, Brandes AA, Gijtenbeek J, Marosi C, Vecht CJ, Mokhtari K, Wesseling P, Villa S, Eisenhauer E, Gorlia T, Weller M, Lacombe D, Cairncross JG, Mirimanoff RO (2009) 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. Lancet Oncol 10(5):459–466. doi: 10.1016/s1470-2045(09)70025-7 PubMedCrossRefGoogle Scholar
  55. 55.
    Schaich M, Kestel L, Pfirrmann M, Robel K, Illmer T, Kramer M, Dill C, Ehninger G, Schackert G, Krex D (2009) A MDR1 (ABCB1) gene single nucleotide polymorphism predicts outcome of temozolomide treatment in glioblastoma patients. Ann Oncol 20(1):175–181. doi: 10.1093/annonc/mdn548 PubMedCrossRefGoogle Scholar
  56. 56.
    Gerstner ER, Yip S, Wang DL, Louis DN, Iafrate AJ, Batchelor TT (2009) Mgmt methylation is a prognostic biomarker in elderly patients with newly diagnosed glioblastoma. Neurology 73(18):1509–1510. doi: 10.1212/WNL.0b013e3181bf9907 PubMedCentralPubMedCrossRefGoogle Scholar
  57. 57.
    Felsberg J, Rapp M, Loeser S, Fimmers R, Stummer W, Goeppert M, Steiger HJ, Friedensdorf B, Reifenberger G, Sabel MC (2009) Prognostic significance of molecular markers and extent of resection in primary glioblastoma patients. Clin Cancer Res 15(21):6683–6693. doi: 10.1158/1078-0432.ccr-08-2801 PubMedCrossRefGoogle Scholar
  58. 58.
    Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, Kros JM, Hainfellner JA, Mason W, Mariani L, Bromberg JE, Hau P, Mirimanoff RO, Cairncross JG, Janzer RC, Stupp R (2005) MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352(10):997–1003. doi: 10.1056/NEJMoa043331 PubMedCrossRefGoogle Scholar
  59. 59.
    Hegi ME, Diserens AC, Godard S, Dietrich PY, Regli L, Ostermann S, Otten P, Van Melle G, de Tribolet N, Stupp R (2004) Clinical trial substantiates the predictive value of O-6-methylguanine-DNA methyltransferase promoter methylation in glioblastoma patients treated with temozolomide. Clin Cancer Res 10(6):1871–1874PubMedCrossRefGoogle Scholar
  60. 60.
    Kim YS, Kim SH, Cho J, Kim JW, Chang JH, Kim DS, Lee KS, Suh CO (2012) MGMT gene promoter methylation as a potent prognostic factor in glioblastoma treated with temozolomide-based chemoradiotherapy: a single-institution study. Int J Radiat Oncol Biol Phys 84(3):661–667. doi: 10.1016/j.ijrobp.2011.12.086 PubMedCrossRefGoogle Scholar
  61. 61.
    Ohka F, Natsume A, Motomura K, Kishida Y, Kondo Y, Abe T, Nakasu Y, Namba H, Wakai K, Fukui T, Momota H, Iwami K, Kinjo S, Ito M, Fujii M, Wakabayashi T (2011) The global DNA methylation surrogate LINE-1 methylation is correlated with MGMT promoter methylation and is a better prognostic factor for glioma. PLoS ONE 6(8):e23332. doi: 10.1371/journal.pone.0023332 PubMedCentralPubMedCrossRefGoogle Scholar
  62. 62.
    Sonoda Y, Kumabe T, Watanabe M, Nakazato Y, Inoue T, Kanamori M, Tominaga T (2009) Long-term survivors of glioblastoma: clinical features and molecular analysis. Acta Neurochir (Wien) 151(11):1349–1358. doi: 10.1007/s00701-009-0387-1 CrossRefGoogle Scholar
  63. 63.
    Cao VT, Jung TY, Jung S, Jin SG, Moon KS, Kim IY, Kang SS, Park CS, Lee KH, Chae HJ (2009) The correlation and prognostic significance of MGMT promoter methylation and MGMT protein in glioblastomas. Neurosurgery 65 (5):866–875; discussion 875. doi: 10.1227/01.NEU.0000357325.90347.A1
  64. 64.
    Watanabe T, Katayama Y, Komine C, Yoshino A, Ogino A, Ohta T, Fukushima T (2005) O6-methylguanine-DNA methyltransferase methylation and TP53 mutation in malignant astrocytomas and their relationships with clinical course. Int J Cancer 113(4):581–587. doi: 10.1002/ijc.20625 PubMedCrossRefGoogle Scholar
  65. 65.
    Sonoda Y, Yokosawa M, Saito R, Kanamori M, Yamashita Y, Kumabe T, Watanabe M, Tominaga T (2010) O(6)-Methylguanine DNA methyltransferase determined by promoter hypermethylation and immunohistochemical expression is correlated with progression-free survival in patients with glioblastoma. Int J Clin Oncol 15(4):352–358. doi: 10.1007/s10147-010-0065-6 PubMedCrossRefGoogle Scholar
  66. 66.
    Chakravarti A, Erkkinen MG, Nestler U, Stupp R, Mehta M, Aldape K, Gilbert MR, Black PM, Loeffler JS (2006) Temozolomide-mediated radiation enhancement in glioblastoma: a report on underlying mechanisms. Clin Cancer Res 12(15):4738–4746. doi: 10.1158/1078-0432.CCR-06-0596 PubMedCrossRefGoogle Scholar
  67. 67.
    Esteller M, Hamilton SR, Burger PC, Baylin SB, Herman JG (1999) Inactivation of the DNA repair gene O6-methylguanine-DNA methyltransferase by promoter hypermethylation is a common event in primary human neoplasia. Cancer Res 59(4):793–797PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Haiyu Yang
    • 1
  • Danping Wei
    • 1
  • Kunxian Yang
    • 3
  • Wenru Tang
    • 1
  • Ying Luo
    • 1
  • Jihong Zhang
    • 1
    • 2
  1. 1.Lab of Molecular Genetics of Aging and Tumor, Faculty of MedicineKunming University of Science and TechnologyKunmingChina
  2. 2.Lab of Molecular Genetics of Aging and Tumor, Faculty of Life Science and TechnologyKunming University of Science and TechnologyKunmingChina
  3. 3.Oncology Department of Breast and Thyroid SurgeryThe First People’s Hospital of Yunnan ProvinceKunmingChina

Personalised recommendations