title: NDRG1 prognosticates the natural course of disease in WHO grade II glioma.
abstract: There is a lack of relevant prognostic and predictive factors in neurooncology besides mutation of isocitrate dehydrogenase 1, codeletion of 1p/19q and promoter hypermethylation of O (6) -methylguanine-DNA-methyltransferase. More importantly, there is limited translation of these factors into clinical practice. The cancer genome atlas data and also clinical correlative analyses suggest a pivotal role for the epidermal growth factor receptor /protein kinase B/mammalian target of rapamycin (mTOR) pathway in both biology and the clinical course of gliomas. However, attempts to stratify gliomas by activating alterations in this pathway have failed thus far. The tumors of 40 patients with WHO grade II gliomas without immediate postoperative genotoxic treatment and known progression and survival status at a median follow-up of 12.2 years were analyzed for expression of the mTOR complex 2 downstream target N-myc downstream regulated gene (NDRG)1 using immunohistochemistry. Baseline characteristics for NDRG1 absent/low versus moderate/high patients were similar. Time to reintervention was significantly longer in the NDRG1 group (P = 0.026). NDRG1 may become a novel biomarker to guide the decision which WHO°II glioma patients may be followed without postsurgical intervention and which patients should receive genotoxic treatment early on. Validation of this hypothesis will be possible with the observational arm of the RTOG 9802 and the pretreatment step of the EORTC 22033/26032 trials.
authors.affiliation: German Cancer Consortium (DKTK), Clinical Cooperation Units Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Blaes
authors.forename: M
authors.initials: M
authors.lastname: Weiler
authors.forename: F
authors.initials: F
authors.lastname: Sahm
authors.forename: B
authors.initials: B
authors.lastname: Hentschel
authors.forename: M
authors.initials: M
authors.lastname: Osswald
authors.forename: M
authors.initials: M
authors.lastname: Czabanka
authors.forename: C M
authors.initials: CM
authors.lastname: Thomé
authors.forename: M G
authors.initials: MG
authors.lastname: Schliesser
authors.forename: S
authors.initials: S
authors.lastname: Pusch
authors.forename: S
authors.initials: S
authors.lastname: Luger
authors.forename: F
authors.initials: F
authors.lastname: Winkler
authors.forename: A
authors.initials: A
authors.lastname: Radbruch
authors.forename: M
authors.initials: M
authors.lastname: Jugold
authors.forename: M
authors.initials: M
authors.lastname: Simon
authors.forename: J P
authors.initials: JP
authors.lastname: Steinbach
authors.forename: G
authors.initials: G
authors.lastname: Schackert
authors.forename: M
authors.initials: M
authors.lastname: Tatagiba
authors.forename: M
authors.initials: M
authors.lastname: Westphal
authors.forename: J C
authors.initials: JC
authors.lastname: Tonn
authors.forename: D
authors.initials: D
authors.lastname: Gramatzki
authors.forename: T
authors.initials: T
authors.lastname: Pietsch
authors.forename: C
authors.initials: C
authors.lastname: Hartmann
authors.forename: H
authors.initials: H
authors.lastname: Glimm
authors.forename: P
authors.initials: P
authors.lastname: Vajkoczy
authors.forename: A
authors.initials: A
authors.lastname: von Deimling
authors.forename: M
authors.initials: M
authors.lastname: Platten
authors.forename: M
authors.initials: M
authors.lastname: Weller
authors.forename: W
authors.initials: W
authors.lastname: Wick
mesh_terms: D000328:Adult; D000368:Aged; D001254:Astrocytoma / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D014408:Biomarkers, Tumor / Q000378:metabolism; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D018797:Cell Cycle Proteins / Q000378:metabolism*; D005500:Follow-Up Studies; D005910:Glioma / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008875:Middle Aged; D060787:Neoplasm Grading; D009837:Oligodendroglioma / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D011379:Prognosis; D011446:Prospective Studies; D019233:Retreatment; D016019:Survival Analysis; D013997:Time Factors; D000099259:N-myc Downstream-Regulated Gene 1 Protein
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D000099259:N-myc Downstream-Regulated Gene 1 Protein