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HDAC4, a prognostic and chromosomal instability marker, refines the predictive value of MGMT promoter methylation.

Cheng W, Li M, Cai J, Wang K, Zhang C, Bao Z, Liu Y, Wu A - J. Neurooncol. (2015)

Bottom Line: The results showed that HDAC4 expression is downregulated in high- as compared to low-grade glioma and is associated with a favorable clinical outcome.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, The First Hospital of China Medical University, Nanjing Street 155, Heping District, Shenyang, 110001, China.

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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Related in: MedlinePlus

HDAC4 expression is negatively correlated with tumor grade. The association between HDAC4 expression level and grade II, III, and IV glioma was evaluated in the CGGA (a) and three other validation sets (b–d)
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Fig1: HDAC4 expression is negatively correlated with tumor grade. The association between HDAC4 expression level and grade II, III, and IV glioma was evaluated in the CGGA (a) and three other validation sets (b–d)

Mentions: To test the relationship between HDAC4 expression and tumor grade, patients were stratified into low or high expression groups according to the median value for HDAC4 expression in each database. The percentage of samples with low expression increased with progressive malignancy (P < 0.001; χ2 test) (Table S1). This correlation between HDAC4 expression and tumor grade was studied in CGGA and three validation sets (Fig. 1a–d) showing that HDAC4 expression differed among various grades and was downregulated for higher grades. Based on these results, we propose that low HDAC4 expression is a characteristic of high-grade glioma.Fig. 1


HDAC4, a prognostic and chromosomal instability marker, refines the predictive value of MGMT promoter methylation.

Cheng W, Li M, Cai J, Wang K, Zhang C, Bao Z, Liu Y, Wu A - J. Neurooncol. (2015)

HDAC4 expression is negatively correlated with tumor grade. The association between HDAC4 expression level and grade II, III, and IV glioma was evaluated in the CGGA (a) and three other validation sets (b–d)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4368847&req=5

Fig1: HDAC4 expression is negatively correlated with tumor grade. The association between HDAC4 expression level and grade II, III, and IV glioma was evaluated in the CGGA (a) and three other validation sets (b–d)
Mentions: To test the relationship between HDAC4 expression and tumor grade, patients were stratified into low or high expression groups according to the median value for HDAC4 expression in each database. The percentage of samples with low expression increased with progressive malignancy (P < 0.001; χ2 test) (Table S1). This correlation between HDAC4 expression and tumor grade was studied in CGGA and three validation sets (Fig. 1a–d) showing that HDAC4 expression differed among various grades and was downregulated for higher grades. Based on these results, we propose that low HDAC4 expression is a characteristic of high-grade glioma.Fig. 1

Bottom Line: The results showed that HDAC4 expression is downregulated in high- as compared to low-grade glioma and is associated with a favorable clinical outcome.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, The First Hospital of China Medical University, Nanjing Street 155, Heping District, Shenyang, 110001, China.

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.

Show MeSH
Related in: MedlinePlus