Global histone modification patterns as prognostic markers to classify glioma patients.
BACKGROUND
An altered pattern of epigenetic modifications is central to the development and progression of various tumors. We studied epigenetic changes involving multiple modifications of histones to better predict prognosis of glioma patients.


METHODS
Immunohistochemistry was done to investigate global histone modification expression of histone 3 lysine 4 dimethylation (H3K4diMe), histone 4 arginine 3 monomethylation (H4R3monoMe), histone 4 lysine 20 trimethylation (H4K20triMe), and acetylation of histone 3 lysine 9 (H3K9Ac), histone 3 lysine 18 (H3K18Ac), histone 4 lysine 12 (H4K12Ac), and histone 4 lysine 16 (H4K16Ac) in resected tumor samples of 230 glioma patients. Data were analyzed using a recursive partitioning analysis (RPA).


RESULTS
RPA classified the patients into 10 distinct prognostic groups based on WHO grade, histology, and histone modifications: H3K9Ac (<88% or ≥88% tumor cells), H3K4diMe (<64% or ≥64% tumor cells), H3K18Ac (<74% or ≥74% tumor cells), and H4K20triMe (<75% or ≥75% tumor cells). The 10 groups were associated with significantly different progression-free (P < 0.0001) and overall survival (P < 0.0001). Cox proportional hazards models including age, sex, WHO grade, histology, extent of tumor resection, Karnofsky performance status score, and RPA groups retained age and RPA groups as the sole independent factors significantly influencing overall survival. For progression-free survival, RPA grouping was the only independent prognostic factor.


CONCLUSIONS
Multiple histone modifications seem to have prognostic relevance in glioma.


CONCLUSIONS
Further evaluation of histone modifications as prognostic markers of treatment and predictors of chemotherapy response using histone deacetylase inhibitors is warranted.
Department of Neurosurgery, Xijing Institute of Clinical Neuroscience, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, People's Republic of China.
Bo-lin
BL
Liu
Jin-xiang
JX
Cheng
Xiang
X
Zhang
Rui
R
Wang
Wei
W
Zhang
Hong
H
Lin
Xian
X
Xiao
Sang
S
Cai
Xiao-yan
XY
Chen
Hong
H
Cheng
D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D001932:Brain Neoplasms / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D018572:Disease-Free Survival; D044127:Epigenesis, Genetic; D005260:Female; D005910:Glioma / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D055815:Young Adult
D014408:Biomarkers, Tumor; D006657:Histones