Classifying lower grade glioma cases according to whole genome gene expression.
OBJECTIVE
To identify a gene-based signature as a novel prognostic model in lower grade gliomas.


RESULTS
A gene signature developed from HOXA7, SLC2A4RG and MN1 could segregate patients into low and high risk score groups with different overall survival (OS), and was validated in TCGA RNA-seq and GSE16011 mRNA array datasets. Receiver operating characteristic (ROC) was performed to show that the three-gene signature was more sensitive and specific than histology, grade, age, IDH1 mutation and 1p/19q co-deletion. Gene Set Enrichment Analysis (GSEA) and GO analysis showed high-risk samples were associated with tumor associated macrophages (TAMs) and highly invasive phenotypes. Moreover, HOXA7-siRNA inhibited migration and invasion in vitro, and downregulated MMP9 at the protein level in U251 glioma cells.


METHODS
A cohort of 164 glioma specimens from the Chinese Glioma Genome Atlas (CGGA) array database were assessed as the training group. TCGA RNA-seq and GSE16011 mRNA array datasets were used for validation. Regression analyses and linear risk score assessment were performed for the identification of the three-gene signature comprising HOXA7, SLC2A4RG and MN1.


CONCLUSIONS
We established a three-gene signature for lower grade gliomas, which could independently predict overall survival (OS) of lower grade glioma patients with higher sensitivity and specificity compared with other clinical characteristics. These findings indicate that the three-gene signature is a new prognostic model that could provide improved OS prediction and accurate therapies for lower grade glioma patients.
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Baoshi
B
Chen
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.|Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.
Tingyu
T
Liang
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.|Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.|Chinese Glioma Cooperative Group (CGCG), China.
Pei
P
Yang
Department of Neurosurgery, Guangdong Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Haoyuan
H
Wang
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.|Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.|Chinese Glioma Cooperative Group (CGCG), China.
Yanwei
Y
Liu
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.|Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.
Fan
F
Yang
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.|Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.|Chinese Glioma Cooperative Group (CGCG), China.
Gan
G
You
D000328:Adult; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D015331:Cohort Studies; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human; D005910:Glioma / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D008297:Male; D060787:Neoplasm Grading; D016019:Survival Analysis; D014162:Transfection
gene signature; lower grade glioma; prognosis; risk score
CNS Neurosci Ther. 2013 Nov;19(11):882-8
23841872
Cancer Lett. 2016 Jun 1;375(2):263-73
26966000
Oncotarget. 2015 Oct 6;6(30):30295-305
26210286
Int J Oncol. 2012 Mar;40(3):825-32
22108652
Clin Cancer Res. 2013 Jul 15;19(14):3776-86
23741072
Nat Rev Cancer. 2005 Nov;5(11):845-56
16239904
Neurology. 2014 Sep 23;83(13):1200-6
25150284
Oncol Rep. 2015 Feb;33(2):990-6
25501982
Transl Res. 2012 Nov;160(5):355-62
22735029
Oncotarget. 2014 Dec 30;5(24):12593-606
25333259
Neuro Oncol. 2012 Dec;14(12):1432-40
23090983
Seizure. 2014 Nov;23(10):844-51
25153654
Oncotarget. 2016 Apr 12;7(15):19519-30
26799586
Sci Rep. 2016 Feb 16;6:21141
26879272
J Exp Clin Cancer Res. 2015 Mar 04;34:23
25880120
J Neurooncol. 2012 Jan;106(2):217-24
21842313
Oncotarget. 2015 Aug 28;6(25):20885-901
26369702
Am J Med Genet A. 2016 Feb;170A(2):498-503
26545049
PLoS One. 2015 Jun 26;10(6):e0130872
26115094
Neurosurg Focus. 2014 Dec;37(6):E13
25434382
Eur J Surg Oncol. 2015 Dec;41(12):1685-90
26454767
Carcinogenesis. 2012 May;33(5):1065-71
22387365
Nucleic Acids Res. 2013 Jan;41(Database issue):D808-15
23203871
Neuro Oncol. 2014 Dec;16(12):1570-4
25355680
Cancer. 2013 Feb 15;119(4):814-24
22990979
J Exp Clin Cancer Res. 2016 Jun 21;35(1):100
27329103
Neuro Oncol. 2012 Jun;14 (6):712-9
22570426
Nat Neurosci. 2016 Jan;19(1):20-7
26713745