Identification of histological markers for malignant glioma by genome-wide expression analysis: dynein, alpha-PIX and sorcin.
Glioblastoma multiforme (GBM), the most malignant class of glial neoplasm (grade IV in WHO criteria), carries the worst clinical prognosis among primary brain tumors in adults. To identify a set of genes involved in the tumorigenesis of GBM, we evaluated expression profiles of GBM tissues from 11 patients using a cDNA microarray representing 25,344 human genes. By comparing the profiles with those of normal brain tissue, we identified a number of differentially expressed genes: 54 with increased expression and 45 with reduced expression in GBMs. Semi-quantitative RT-PCR experiments with 6 of those genes confirmed higher expression of DNCH2, ARHGEF6, NPM1 and SRI and lower expression of NRGN and TM4SF2 in GBM tumors. Immunohistochemical staining for 3 of the respective gene products, dynein (product of DNCH2), alpha-PIX (product of ARHGEF6), and sorcin (product of SRI) indicated that this technique might be useful for histological grading of glial tumors. To establish criteria for this diagnostic approach, we scored glial tumor tissues of different histological grades according to the staining results; the scores were significantly higher in anaplastic astrocytomas and GBMs than in diffuse astrocytomas or normal brain tissues. These findings indicated that levels of these three proteins might serve as histological markers for malignant glioma classification.
Yokota
Takashi
T
Department of Molecular Biology, Institute of Gerontology. Nippon Medical School, 1-396, Kosugi-cho, Nakahara-ku, 211-8533, Kawasaki, Japan. taka@nms.ac.jp
Kouno
Jun
J
Adachi
Koji
K
Takahashi
Hiroshi
H
Teramoto
Akira
A
Matsumoto
Koshi
K
Sugisaki
Yuichi
Y
Onda
Masamitsu
M
Tsunoda
Tatsuhiko
T
D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D001932:Brain Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D002135:Calcium-Binding Proteins / Q000032:analysis / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000032:analysis / Q000235:genetics*; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics; D004398:Dyneins / Q000032:analysis / Q000235:genetics*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D020662:Guanine Nucleotide Exchange Factors / Q000032:analysis / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D009367:Neoplasm Staging; D000090243:Nucleophosmin; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D064067:Rho Guanine Nucleotide Exchange Factors
C576603:ARHGEF6 protein, human; D014408:Biomarkers, Tumor; D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; D004273:DNA, Neoplasm; D020662:Guanine Nucleotide Exchange Factors; C000716967:NPM1 protein, human; D064067:Rho Guanine Nucleotide Exchange Factors; C503113:SRI protein, human; D000090243:Nucleophosmin; D004398:Dyneins