HDAC4, a Prognostic and Chromosomal Instability Marker, Refines the Predictive Value of MGMT Promoter Methylation

Overview

Journal J Neurooncol

Publisher Springer

Date 2015 Jan 6

PMID 25557107

Citations 23

Authors

Wen Cheng

Mingyang Li

Jinquan Cai

Kuanyu Wang

Chuanbao Zhang

Zhaoshi Bao

Yanwei Liu

Anhua Wu

Affiliations

Soon will be listed here.

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.

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