title: Association between small heat shock protein B11 and the prognostic value of MGMT promoter methylation in patients with high-grade glioma.
abstract: OBJECT This study investigated the role and prognostic value of heat shock proteins (HSPs) in glioma. METHODS Data from 3 large databases of glioma samples (Chinese Glioma Genome Atlas, Repository for Molecular Brain Neoplasia Data, and GSE16011), which contained whole-genome messenger RNA microarray expression data and patients' clinical data, were analyzed. Immunohistochemical analysis was performed to validate protein expression in another set of 50 glioma specimens. RESULTS Of 28 HSPs, 11 were overexpressed in high-grade glioma (HGG) compared with low-grade glioma. A univariate Cox analysis revealed that HSPB11 has significant prognostic value for each glioma grade, which was validated by a Kaplan-Meier survival analysis. HSPB11 expression was associated with poor prognosis and was independently correlated with overall survival (OS) in HGG. This study further explored the combined role of HSPB11 and other molecular markers in HGG, such as isocitrate dehydrogenase 1 (IDH1) mutation and O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation status. HSPB11 expression was able to refine the prognostic value of IDH1 mutation in patients with HGG. However, when combined with MGMT promoter methylation status, among patients with a methylated MGMT promoter, those with lower levels of HSPB11 expression had longer OS and progression-free survival than patients with higher levels of HSPB11 expression or with an unmethylated MGMT promoter. Moreover, within the MGMT promoter methylation group, patients with low levels of HSPB11 expression were more sensitive to combined radiochemotherapy than those with high levels of HSPB11 expression, which may explain why some patients with HGG with a methylated MGMT promoter show tolerance to radiochemotherapy. CONCLUSIONS HSPB11 was identified as a novel prognostic marker in patients with HGG. Together with MGMT promoter methylation status, HSPB11 expression can predict outcome for patients with HGG and identify those who would most benefit from combined radiochemotherapy.
authors.affiliation: Department of Neurosurgery, 1 The First Hospital of China Medical University, Shenyang;|Chinese Glioma Cooperative Group, Beijing, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Cheng
authors.affiliation: Beijing Tiantan Hospital, Capital Medical University;|Beijing Neurosurgical Institute; and.|Chinese Glioma Cooperative Group, Beijing, China.
authors.forename: Mingyang
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, 1 The First Hospital of China Medical University, Shenyang;|Chinese Glioma Cooperative Group, Beijing, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Beijing Neurosurgical Institute; and.|Chinese Glioma Cooperative Group, Beijing, China.
authors.forename: Chuanbao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: The Second Affiliated Hospital of Harbin Medical University, Harbin;|Chinese Glioma Cooperative Group, Beijing, China.
authors.forename: Jinquan
authors.initials: J
authors.lastname: Cai
authors.affiliation: The First Affiliated Hospital of Dalian Medical University, Dalian;|Chinese Glioma Cooperative Group, Beijing, China.
authors.forename: Kuanyu
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, 1 The First Hospital of China Medical University, Shenyang;|Chinese Glioma Cooperative Group, Beijing, China.
authors.forename: Anhua
authors.initials: A
authors.lastname: Wu
mesh_terms: D001932:Brain Neoplasms / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D059248:Chemoradiotherapy; D005260:Female; D005910:Glioma / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D007521:Isocitrate Dehydrogenase; D008297:Male; D060787:Neoplasm Grading; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000378:metabolism; D011237:Predictive Value of Tests; D011379:Prognosis; D011401:Promoter Regions, Genetic; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: C525841:HSPB11 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D007521:Isocitrate Dehydrogenase; D019853:O(6)-Methylguanine-DNA Methyltransferase
keywords: CGGA = Chinese Glioma Genome Atlas; GBM = glioblastoma; GO = gene ontology; GSEA = Gene Set Enrichment Analysis; HGG = high-grade glioma; HSP = heat shock protein; HSPB11; IDH1 = isocitrate dehydrogenase 1; KPS = Karnofsky Performance Scale; LGG = low-grade glioma; MGMT promoter methylation; MGMT= O6-methylguanine-DNA methyltransferase; OS = overall survival; PCR = polymerase chain reaction; PFS = progression-free survival; REMBRANDT = Repository for Molecular Brain Neoplasia Data; SAM = significance analysis of microarrays; TMZ = temozolomide; glioma; mRNA = messenger RNA; oncology; prognosis