TLR9 expression in glioma tissues correlated to glioma progression and the prognosis of GBM patients.
BACKGROUND
Our study aims to evaluate the expression of TLR9 in glioma tissues, examine the association between TLR9 expression, clinicopathological variables, and glioma patient outcome, we further characterized the direct effects of TLR9 agonist CpG ODN upon the proliferation and invasion of glioma cells in vitro.


METHODS
RT-PCR and immunofluorescence were used to determine the expression of TLR9 in glioma cell lines and clinical glioma samples. Tissue microarry and immunohistochemistry were applied to evaluated TLR9 expression in 292 newly diagnosed glioma and 13 non-neoplastic brain tissues. We further investigated the effect of CpG ODN on the proliferation and invasion of glioma cells in vitro with MTT assays and matrigel transwell assay respectively.


RESULTS
RT-PCR showed that TLR9 expressed in all the glioma samples and glioma cell lines we examined. The tissue array analysis indicated that TLR9 expression is correlated with malignancy of glioma (p < 0.01). Multivariate Cox regression analysis revealed that TLR9 expression is an independent prognostic factor for PFS of GBM patients (P = 0.026). TLR9 agonist CpG ODN has no significant effect on glioma proliferation, but matrigel transwell analysis showed that TLR9 agonist CpG ODN can significantly enhance glioma invasion in vitro.


CONCLUSIONS
Our data indicated that TLR9 expression increases according to the histopathological grade of glioma, and the TLR9 expression level is related to the PFS of GBM patients. In addition, our findings warrant caution in the directly injection of TLR9 agonist CpG ODN into glioma tissues for the glioma immunotherapy.
Wang
Chao
C
Department of Neurosurgery, The First Affiliated Hospital of China Medical University, Shenyang, China.
Cao
Shouqiang
S
Yan
Ying
Y
Ying
Qiao
Q
Jiang
Tao
T
Xu
Ke
K
Wu
Anhua
A
D000328:Adult; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D005455:Fluorescent Antibody Technique; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D046888:Tissue Array Analysis; D051217:Toll-Like Receptor 9 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
C408982:CPG-oligonucleotide; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9