From: Subject: Oncogene - Abstract of article: Identification of expressed genes characterizing long-term survival in malignant glioma patients Date: Sat, 13 May 2006 13:05:47 +0200 MIME-Version: 1.0 Content-Type: multipart/related; type="text/html"; boundary="----=_NextPart_000_0000_01C6768D.F38035D0" X-MimeOLE: Produced By Microsoft MimeOLE V6.00.2900.2869 This is a multi-part message in MIME format. ------=_NextPart_000_0000_01C6768D.F38035D0 Content-Type: text/html; charset="iso-8859-1" Content-Transfer-Encoding: quoted-printable Content-Location: http://www.nature.com/onc/journal/vaop/ncurrent/abs/1209585a.html Oncogene - Abstract = of article: Identification of expressed genes characterizing long-term = survival in malignant glioma patients
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Original Article

Oncogene advance online publication = 1 May 2006; doi:=20 10.1038/sj.onc.1209585

Identification of expressed genes characterizing long-term = survival=20 in malignant glioma patients

R Yamanaka1,=20 T Arao2,=20 N Yajima1,=20 N Tsuchiya1,=20 J Homma1,=20 R Tanaka1,=20 M Sano1,=20 A Oide3,=20 M Sekijima3=20 and K Nishio2

  1. 1Department of Neurosurgery, Brain Research = Institute,=20 Niigata University, Niigata City, Japan
  2. 2Pharmacology Division, National Cancer = Center Research=20 Institute, Chuo-ku, Tokyo, Japan
  3. 3Mitsubishi Chemical Safety Institute, = Ibaraki,=20 Japan

Correspondence: Dr R Yamanaka, Department of = Neurosurgery, Brain=20 Research Institute, Niigata University, Asahimachi-dori 1-757, Niigata = City=20 951-8585, Japan. E-mail: ryaman@bri.niigata-u.ac.jp=

Received 7 November 2005; Revised=20 8 March 2006; Accepted 8 March 2006; Published = online=20 1 May 2006.

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Abstract

Better understanding of the underlying biology of = malignant=20 gliomas is critical for the development of early detection strategies = and new=20 therapeutics. This study aimed to define genes associated with survival. = We=20 investigated whether genes coupled with a class prediction model could = be used=20 to define subgroups of high-grade gliomas in a more objective manner = than=20 standard pathology. RNAs from 29 malignant gliomas were analysed using = Agilent=20 microarrays. We identified 21 genes whose expression was most strongly = and=20 consistently related to patient survival based on univariate = proportional=20 hazards models. In six out of 10 genes, changes in gene expression were=20 validated by quantitative real-time PCR. After adjusting for clinical = covariates=20 based on a multivariate analysis, we finally obtained a statistical = significance=20 level for DDR1 (discoidin domain receptor family, member 1), = DYRK3=20 (dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 3) and=20 KSP37 (Ksp37 protein). In independent samples, it was confirmed = that DDR1=20 protein expression was also correlated to the prognosis of glioma = patients=20 detected by immunohistochemical staining. Furthermore, we analysed the = efficacy=20 of the short interfering RNA (siRNA)-mediated inhibition of DDR1 mRNA = synthesis=20 in glioma cell lines. Cell proliferation and invasion were significantly = suppressed by siRNA against DDR1. Thus, DDR1 can be a novel molecular = target of=20 therapy as well as an important predictive marker for survival in = patients with=20 glioma. Our method was effective at classifying high-grade gliomas = objectively,=20 and provided a more accurate predictor of prognosis than histological=20 grading.

Keywords:

cDNA array, gene expression profiles, glioma, = survival=20 predictor, siRNA

Abbreviations:

ALCAM, activated leukocyte cell adhesion = molecule; cDNA,=20 complementary DNA; Cy, cyanine; DDR1, discoidin domain receptor family, = member=20 1; DYRK3, dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase = 3; FBS,=20 fetal bovine serum; ITGA5, integrin alpha 5; ITGB2, integrin beta 2; = KSP37,=20 Ksp37 protein; LDHC, lactate dehydrogenase C; LOC340371, hypothetical = protein=20 LOC340371; MEM, minimum essential medium; PBS, phosphate-buffered = saline;=20 SLC2A3, solute carrier family 2 member 3; SLN, sarcolipin; s.d., = standard=20 deviation; siRNA, short interfering RNA

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Oncogene

ISSN: 0950-9232

EISSN: 1476-5594

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