title: HDAC4, a prognostic and chromosomal instability marker, refines the predictive value of MGMT promoter methylation.
abstract: Chromosomal instability is a hallmark of human cancers and is closely linked to tumorigenesis. The prognostic value of molecular signatures of chromosomal instability (CIN) has been validated in various cancers. However, few studies have examined the relationship between CIN and glioma. Histone deacetylases (HDACs) regulate chromosome structure and are linked to the loss of genomic integrity in cancer cells. In this study, the prognostic value of HDAC4 expression and its association with markers of CIN were investigated by analyzing data from our own and four other large sample databases. The results showed that HDAC4 expression is downregulated in high- as compared to low-grade glioma and is associated with a favorable clinical outcome. HDAC4 expression and CIN were closely related in glioma from both functional and statistical standpoints. Moreover, the predictive value of the O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status-a widely used glioma marker-was refined by HDAC4 expression level, which was significantly related to CIN in our study. In conclusion, we propose that HDAC4 expression, a prognostic and CIN marker, enhances the predictive value of MGMT promoter methylation status for identifying patients who will most benefit from radiochemotherapy.
authors.affiliation: Department of Neurosurgery, The First Hospital of China Medical University, Nanjing Street 155, Heping District, Shenyang, 110001, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Cheng
authors.forename: Mingyang
authors.initials: M
authors.lastname: Li
authors.forename: Jinquan
authors.initials: J
authors.lastname: Cai
authors.forename: Kuanyu
authors.initials: K
authors.lastname: Wang
authors.forename: Chuanbao
authors.initials: C
authors.lastname: Zhang
authors.forename: Zhaoshi
authors.initials: Z
authors.lastname: Bao
authors.forename: Yanwei
authors.initials: Y
authors.lastname: Liu
authors.forename: Anhua
authors.initials: A
authors.lastname: Wu
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics*; D018450:Disease Progression; D005910:Glioma / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism*; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D060787:Neoplasm Grading; D011379:Prognosis; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000378:metabolism*; D016019:Survival Analysis; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D002843:Chromatin; D012097:Repressor Proteins; D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; C400300:HDAC4 protein, human; D006655:Histone Deacetylases; D045643:DNA Repair Enzymes