Abstract
Previous studies showed that isocitrate dehydrogenase 1 (IDH1) mutation might be a prognostic biomarker of prognosis in glioblastoma (GBM) patients, but the outcomes were various. A meta-analysis of published studies was carried out to reach a reliable assessment of the association between IDH1 mutation and mortality of GBM patients. Relative risks (RRs) with 95% confidence intervals (95%CIs) were pooled using meta-analysis to assess risk of mortality in patients with IDH1 mutation. A total of 20 studies (3 prospective cohort and 17 retrospective cohort studies) were finally included into the meta-analysis. Meta-analysis of total included studies suggested that GBM patients with IDH1 mutation had decreased risk of mortality compared those patients without IDH1 mutation (RR = 0.43, 95%CI 0.35–0.54, P < 0.001). GBM patients with IDH1 mutation from European countries had also decreased mortality risk compared with those patients without IDH1 mutation (RR = 0.35, 95%CI 0.25–0.49, P < 0.001), but GBM patients with IDH1 mutation from Asians only dad 32 % decrease of mortality risk compared with those patients without IDH1 mutation (RR = 0.68, 95%CI 0.49–0.94, P = 0.018). The findings from the meta-analysis provide strong evidence for the association between IDH1 mutation and decreased mortality risk of GBM patients. In addition, there is an obvious difference in the mortality risk of GBM patients with IDH1 mutation between western and eastern countries.
Similar content being viewed by others
References
Omuro A, De Angelis LM (2013) Glioblastoma and other malignant gliomas: a clinical review. JAMA 310(17):1842–1850
Weller M, van den Bent M, Hopkins K, Tonn JC, Stupp R, Falini A, Cohen-Jonathan-Moyal E, Frappaz D, Henriksson R, Balana C, Chinot O, Ram Z, Reifenberger G, Soffietti R, Wick W (2014) EANO guideline for the diagnosis and treatment of anaplastic gliomas and glioblastoma. Lancet Oncol 15(9):e395–e403
Gilbert MR, Dignam JJ, Armstrong TS, Wefel JS, Blumenthal DT, Vogelbaum MA, Colman H, Chakravarti A, Pugh S, Won M, Jeraj R, Brown PD, Jaeckle KA, Schiff D, Stieber VW, Brachman DG, Werner-Wasik M, Tremont-Lukats IW, Sulman EP, Aldape KD, Curran WJ Jr, Mehta MP (2014) A randomized trial of bevacizumab for newly diagnosed glioblastoma. N Engl J Med 370(8):699–708
Kubben PL, ter Meulen KJ, Schijns OE, ter Laak-Poort MP, van Overbeeke JJ, van Santbrink H (2011) Intraoperative MRI-guided resection of glioblastoma multiforme: a systematic review. Lancet Oncol 12(11):1062–1070
Brennan CW, Verhaak RG, McKenna A, Campos B, Noushmehr H, Salama SR, Zheng S, Chakravarty D, Sanborn JZ, Berman SH, Beroukhim R, Bernard B, Wu CJ, Genovese G, Shmulevich I, Barnholtz-Sloan J, Zou L, Vegesna R, Shukla SA, Ciriello G, Yung WK, Zhang W, Sougnez C, Mikkelsen T, Aldape K, Bigner DD, Van Meir EG, Prados M, Sloan A, Black KL, Eschbacher J, Finocchiaro G, Friedman W, Andrews DW, Guha A, Iacocca M, O′Neill BP, Foltz G, Myers J, Weisenberger DJ, Penny R, Kucherlapati R, Perou CM, Hayes DN, Gibbs R, Marra M, Mills GB, Lander E, Spellman P, Wilson R, Sander C, Weinstein J, Meyerson M, Gabriel S, Laird PW, Haussler D, Getz G, Chin L (2013) The somatic genomic landscape of glioblastoma. Cell 155(2):462–477
Patel AP, Tirosh I, Trombetta JJ, Shalek AK, Gillespie SM, Wakimoto H, Cahill DP, Nahed BV, Curry WT, Martuza RL, Louis DN, Rozenblatt-Rosen O, Suva ML, Regev A, Bernstein BE (2014) Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma. Science 344(6190):1396–1401
Sturm D, Bender S, Jones DT, Lichter P, Grill J, Becher O, Hawkins C, Majewski J, Jones C, Costello JF, Iavarone A, Aldape K, Brennan CW, Jabado N, Pfister SM (2014) Paediatric and adult glioblastoma: multiform (epi) genomic culprits emerge. Nat Rev Cancer 14(2):92–107
Reitman ZJ, Yan H (2010) Isocitrate dehydrogenase 1 and 2 mutations in cancer: alterations at a crossroads of cellular metabolism. J Natl Cancer Inst 102(13):932–941
Turcan S, Rohle D, Goenka A, Walsh LA, Fang F, Yilmaz E, Campos C, Fabius AW, Lu C, Ward PS, Thompson CB, Kaufman A, Guryanova O, Levine R, Heguy A, Viale A, Morris LG, Huse JT, Mellinghoff IK, Chan TA (2012) IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype. Nature 483(7390):479–483
Lu C, Ward PS, Kapoor GS, Rohle D, Turcan S, Abdel-Wahab O, Edwards CR, Khanin R, Figueroa ME, Melnick A, Wellen KE, O′Rourke DM, Berger SL, Chan TA, Levine RL, Mellinghoff IK, Thompson CB (2012) IDH mutation impairs histone demethylation and results in a block to cell differentiation. Nature 483(7390):474–478
Sasaki M, Knobbe CB, Munger JC, Lind EF, Brenner D, Brustle A, Harris IS, Holmes R, Wakeham A, Haight J, You-Ten A, Li WY, Schalm S, Su SM, Virtanen C, Reifenberger G, Ohashi PS, Barber DL, Figueroa ME, Melnick A, Zuniga-Pflucker JC, Mak TW (2012) IDH1 (R132H) mutation increases murine haematopoietic progenitors and alters epigenetics. Nature 488(7413):656–659
Parsons DW, Jones S, Zhang X, Lin JC, Leary RJ, Angenendt P, Mankoo P, Carter H, Siu IM, Gallia GL, Olivi A, McLendon R, Rasheed BA, Keir S, Nikolskaya T, Nikolsky Y, Busam DA, Tekleab H, Diaz LA Jr, Hartigan J, Smith DR, Strausberg RL, Marie SK, Shinjo SM, Yan H, Riggins GJ, Bigner DD, Karchin R, Papadopoulos N, Parmigiani G, Vogelstein B, Velculescu VE, Kinzler KW (2008) An integrated genomic analysis of human glioblastoma multiforme. Science 321(5897):1807–1812
Sanson M, Marie Y, Paris S, Idbaih A, Laffaire J, Ducray F, El Hallani S, Boisselier B, Mokhtari K, Hoang-Xuan K, Delattre JY (2009) Isocitrate dehydrogenase 1 codon 132 mutation is an important prognostic biomarker in gliomas. J Clin Oncol 27(25):4150–4154
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
Hartmann C, Hentschel B, Wick W, Capper D, Felsberg J, Simon M, Westphal M, Schackert G, Meyermann R, Pietsch T, Reifenberger G, Weller M, Loeffler M, von Deimling A (2010) Patients with IDH1 wild type anaplastic astrocytomas exhibit worse prognosis than IDH1-mutated glioblastomas, and IDH1 mutation status accounts for the unfavorable prognostic effect of higher age: implications for classification of gliomas. Acta Neuropathol 120(6):707–718
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. AJNR Am J Neuroradiol 33(7):1349–1355
Juratli TA, Kirsch M, Geiger K, Klink B, Leipnitz E, Pinzer T, Soucek S, Schrock E, Schackert G, Krex D (2012) The prognostic value of IDH mutations and MGMT promoter status in secondary high-grade gliomas. J Neurooncol 110(3):325–333
Phillips JJ, Aranda D, Ellison DW, Judkins AR, Croul SE, Brat DJ, Ligon KL, Horbinski C, Venneti S, Zadeh G, Santi M, Zhou S, Appin CL, Sioletic S, Sullivan LM, Martinez-Lage M, Robinson AE, Yong WH, Cloughesy T, Lai A, Phillips HS, Marshall R, Mueller S, Haas-Kogan DA, Molinaro AM, Perry A (2013) PDGFRA amplification is common in pediatric and adult high-grade astrocytomas and identifies a poor prognostic group in IDH1 mutant glioblastoma. Brain Pathol 23(5):565–573
Shin JH, Lee YS, Hong YK, Kang CS (2013) Correlation between the prognostic value and the expression of the stem cell marker CD133 and isocitrate dehydrogenase1 in glioblastomas. J Neurooncol 115(3):333–341
Labussiere M, Boisselier B, Mokhtari K, Di Stefano AL, Rahimian A, Rossetto M, Ciccarino P, Saulnier O, Paterra R, Marie Y, Finocchiaro G, Sanson M (2014) Combined analysis of TERT, EGFR, and IDH status defines distinct prognostic glioblastoma classes. Neurology 83(13):1200–1206
Molenaar RJ, Verbaan D, Lamba S, Zanon C, Jeuken JW, Boots-Sprenger SH, Wesseling P, Hulsebos TJ, Troost D, van Tilborg AA, Leenstra S, Vandertop WP, Bardelli A, van Noorden CJ, Bleeker FE (2014) The combination of IDH1 mutations and MGMT methylation status predicts survival in glioblastoma better than either IDH1 or MGMT alone. Neuro Oncol 16(9):1263–1273
Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327(7414):557–560
DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7(3):177–188
Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315(7109):629–634
Bleeker FE, Atai NA, Lamba S, Jonker A, Rijkeboer D, Bosch KS, Tigchelaar W, Troost D, Vandertop WP, Bardelli A, Van Noorden CJ (2010) The prognostic IDH1 (R132) mutation is associated with reduced NADP + -dependent IDH activity in glioblastoma. Acta Neuropathol 119(4):487–494
Castells X, Acebes JJ, Majos C, Boluda S, Julia-Sape M, Candiota AP, Arino J, Barcelo A, Arus C (2012) Development of robust discriminant equations for assessing subtypes of glioblastoma biopsies. Br J Cancer 106(11):1816–1825
Killela PJ, Pirozzi CJ, Healy P, Reitman ZJ, Lipp E, Rasheed BA, Yang R, Diplas BH, Wang Z, Greer PK, Zhu H, Wang CY, Carpenter AB, Friedman H, Friedman AH, Keir ST, He J, He Y, McLendon RE, Herndon JE 2nd, Yan H, Bigner DD (2014) Mutations in IDH1, IDH2, and in the TERT promoter define clinically distinct subgroups of adult malignant gliomas. Oncotarget 5(6):1515–1525
Mukasa A, Takayanagi S, Saito K, Shibahara J, Tabei Y, Furuya K, Ide T, Narita Y, Nishikawa R, Ueki K, Saito N (2012) Significance of IDH mutations varies with tumor histology, grade, and genetics in Japanese glioma patients. Cancer Sci 103(3):587–592
Stancheva G, Goranova T, Laleva M, Kamenova M, Mitkova A, Velinov N, Poptodorov G, Mitev V, Kaneva R, Gabrovsky N (2014) IDH1/IDH2 but not TP53 mutations predict prognosis in Bulgarian glioblastoma patients. Biomed Res Int 2014654727
Takahashi Y, Nakamura H, Makino K, Hide T, Muta D, Kamada H, Kuratsu J (2013) Prognostic value of isocitrate dehydrogenase 1, O6-methylguanine-DNA methyltransferase promoter methylation, and 1p19q co-deletion in Japanese malignant glioma patients. World J Surg Oncol 11284
Wang XW, Boisselier B, Rossetto M, Marie Y, Idbaih A, Mokhtari K, Gousias K, Hoang-Xuan K, Delattre JY, Simon M, Labussiere M, Sanson M (2013) Prognostic impact of the isocitrate dehydrogenase 1 single-nucleotide polymorphism rs11554137 in malignant gliomas. Cancer 119(4):806–813
Wang Y, Li S, Zhang A, Chen X, You G, Yang P, Yan W, Bao Z, Yao K, Wang L, Li M, Jiang T (2012) Surgical extent impacts the value of the established prognosticators in glioblastoma patients: a prospective translational study in Asia. Head Neck Oncol 4(4):80
Yan W, Zhang W, You G, Bao Z, Wang Y, Liu Y, Kang C, You Y, Wang L, Jiang T (2012) Correlation of IDH1 mutation with clinicopathologic factors and prognosis in primary glioblastoma: a report of 118 patients from China. PLoS ONE 7(1):e30339
Zhang W, Zhang J, Yan W, You G, Bao Z, Li S, Kang C, Jiang C, You Y, Zhang Y, Chen CC, Song SW, Jiang T (2013) Whole-genome microRNA expression profiling identifies a 5-microRNA signature as a prognostic biomarker in Chinese patients with primary glioblastoma multiforme. Cancer 119(4):814–824
Conflict of Interest
None declared.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Dai, Y., Ning, X., Han, G. et al. Assessment of the Association between Isocitrate Dehydrogenase 1 Mutation and Mortality Risk of Glioblastoma Patients. Mol Neurobiol 53, 1501–1508 (2016). https://doi.org/10.1007/s12035-015-9104-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12035-015-9104-7