Histone deacetylase (HDAC)-1, -2, -4 and -6 expression in human pancreatic adenocarcinoma: associations with clinicopathological parameters, tumor proliferative capacity and patients' survival.

Abstract

BACKGROUND:

Histone deacetylases (HDACs) have been associated with malignant tumor development and progression in humans. HDAC inhibitors (HDACIs) are currently being explored as anti-cancer agents in clinical trials. The present study aimed to evaluate the clinical significance of HDAC-1, -2, -4 and -6 protein expression in pancreatic adenocarcinoma.

METHODS:

HDAC-1, -2, -4 and -6 protein expression was assessed immunohistochemically on 70 pancreatic adenocarcinoma tissue specimens and was statistically analyzed with clinicopathological characteristics and patients' survival.

RESULTS:

Enhanced HDAC-1 expression was significantly associated with increased tumor proliferative capacity (p = 0.0238) and borderline with the absence of lymph node metastases (p = 0.0632). Elevated HDAC-4 expression was significantly associated with the absence of organ metastases (p = 0.0453) and borderline with the absence of lymph node metastases (p = 0.0571) and tumor proliferative capacity (p = 0.0576). Enhanced HDAC-6 expression was significantly associated with earlier histopathological stage (p = 0.0115) and borderline with smaller tumor size (p = 0.0864). Pancreatic adenocarcinoma patients with enhanced HDAC-1 and -6 expression showed significantly longer survival times compared to those with low expression (p = 0.0022 and p = 0.0113, respectively), while a borderline association concerning HDAC-2 expression was noted (p = 0.0634).

CONCLUSIONS:

The present study suggested that HDACs may be implicated in pancreatic malignant disease progression, being considered of clinical utility with potential use as therapeutic targets.

• Authors: Constantinos Giaginis, Christos Damaskos, Ioannis Koutsounas, Adamantia Zizi-Serbetzoglou, Nicolaos Tsoukalas, Efstratios Patsouris, Gregorios Kouraklis, Stamatios Theocharis
• Journal: BMC gastroenterology (BMC Gastroenterol) Vol. 15 Pg. 148 (Oct 26 2015) ISSN: 1471-230X [Electronic] England
• PMID: 26502922 (Publication Type: Journal Article)

Chemical References

• Biomarkers, Tumor
• Repressor Proteins
• HDAC1 protein, human
• HDAC2 protein, human
• HDAC4 protein, human
• HDAC6 protein, human
• Histone Deacetylase 1
• Histone Deacetylase 2
• Histone Deacetylase 6
• Histone Deacetylases

Topics

• Adenocarcinoma (enzymology, genetics, mortality, pathology)
• Aged
• Biomarkers, Tumor (genetics, metabolism)
• Cell Proliferation (genetics)
• Female
• Gene Expression
• Histone Deacetylase 1 (metabolism)
• Histone Deacetylase 2 (metabolism)
• Histone Deacetylase 6
• Histone Deacetylases (metabolism)
• Humans
• Male
• Middle Aged
• Neoplasm Metastasis (genetics)
• Pancreatic Neoplasms (enzymology, genetics, mortality, pathology)
• Repressor Proteins (metabolism)