Gene expression profiling and identification of novel prognostic marker genes in neuroblastoma.
To investigate the various genetic characteristics of and differences between early- and advanced-stage neuroblastoma (NB) and to identify candidate genes involved in NB progression, we performed DNA microarray analysis on 20 primary tumors. Two-way clustering analysis based on the expression pattern of approximately 500 of 1,700 genes revealed genetic subgroups in these NB tumors. Although 9 of the 13 early-stage tumors (69%) and 4 of the 6 advanced-stage tumors (67%) were classified as being in the same cluster, the remaining tumors showed different expression profiles. This indicates that both the early- and advanced-stage tumors were heterogeneous. Based on the microarray data, we identified the BIRC, CDKN2D, and SMARCD3 genes as those that are predominantly expressed in either the early or the advanced stage of NB. These genes have been reported to be associated with apoptosis, cell cycles, and the transcriptional activator, respectively. To better assess the prognostic value of the expression of these genes in NB, real-time polymerase chain reaction was carried out on 50 primary tumors. The expression of both the BIRC3 and CDKN2D genes was significantly higher in the early-stage group than in the advanced-stage group (P = 0.002 and 0.003, respectively), whereas the expression of the SMARCD3 gene was significantly reduced in the early-stage group (P = 0.02). Therefore, the BIRC, CDKN2D, and SMARCD3 genes are possible candidates for being novel prognostic markers for NB.
Takita
Junko
J
Department of Pediatrics, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
Ishii
Masami
M
Tsutsumi
Shuichi
S
Tanaka
Yukichi
Y
Kato
Keisuke
K
Toyoda
Yasunori
Y
Hanada
Ryoji
R
Yamamoto
Keiko
K
Hayashi
Yasuhide
Y
Aburatani
Hiroyuki
H
D014408:Biomarkers, Tumor / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002868:Chromosomal Proteins, Non-Histone; D016000:Cluster Analysis; D050764:Cyclin-Dependent Kinase Inhibitor p19; D020869:Gene Expression Profiling / Q000379:methods* / Q000706:statistics & numerical data; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D021621:Imaging, Three-Dimensional / Q000379:methods / Q000706:statistics & numerical data; D007223:Infant; D007231:Infant, Newborn; D051034:Inhibitor of Apoptosis Proteins; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000235:genetics* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods* / Q000706:statistics & numerical data; D016133:Polymerase Chain Reaction / Q000379:methods / Q000706:statistics & numerical data; D011379:Prognosis; D011506:Proteins / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; C493974:CDKN2D protein, human; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D050764:Cyclin-Dependent Kinase Inhibitor p19; D051034:Inhibitor of Apoptosis Proteins; D011506:Proteins; D012334:RNA, Neoplasm; C109786:SMARCD1 protein, human; C491649:SMARCD3 protein, human; D014157:Transcription Factors