Selection of surrogate marker genes in primary central nervous system lymphomas for radio-chemotherapy by DNA array analysis of gene expression profiles.
Primary central nervous system lymphomas (PCNSLs) are extra nodal B-cell non-Hodgkin's lymphomas with primary manifestation in the brain, and their incidence has been increasing among both immunocompetent and immunocompromised populations. Samples of oligodendroglioma (n=5), glioblastoma (n=7), PCNSL (n=6), and normal brain (n=3) were studied (total of 21 samples) using cDNA array technology. The hierarchical clustering algorithm was used to obtain a phylogenetic tree, and it revealed a striking feature: PCNSL was clearly separated. The genes encoding laminin receptor 2, thioredoxin peroxidase, and elongation factor-1 were selected as specific genes in PCNSL by principal component analysis (PCA). When Mann-Whitney tests were performed to identify genes responsible for the differences between responders and non-responders to the treatment schedule for PCNSL, 76 known genes were found to show significantly different expression patterns between the two groups at the P<0.01 level. The two groups were clearly separated by the re-clustering method using the selected genes related to response to chemo-radiotherapy. This is the first report describing the gene expression profiles of PCNSL. In conclusion, accumulation of data with respect to the expression profiles of PCNSL specimens, clinicopathological data, susceptibility to treatment, and outcome will provide information for identifying optimal therapeutic modalities for individual patients and novel therapeutic targets.
Yamanaka
Ryuya
R
Department of Neurosurgery, Brain Research Institute, Niigata University, Niigata City 951-8122, Japan.
Akutagawa
Shigeru
S
Taguchi
Fumiko
F
Yajima
Naoki
N
Tsuchiya
Naoto
N
Uzuka
Takeo
T
Morii
Ken
K
Takahashi
Hideaki
H
Tanaka
Ryuichi
R
Saijo
Nagahiro
N
Nishio
Kazuto
K
D000328:Adult; D000368:Aged; D000465:Algorithms; D001921:Brain / Q000473:pathology; D016543:Central Nervous System Neoplasms / Q000235:genetics* / Q000628:therapy*; D003131:Combined Modality Therapy; D004260:DNA Repair; D018076:DNA, Complementary / Q000378:metabolism; D005260:Female; D006801:Humans; D008223:Lymphoma / Q000235:genetics* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D005810:Multigene Family; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012313:RNA / Q000737:chemistry; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018076:DNA, Complementary; D012313:RNA