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

BMC Gastroenterol. 2015 Oct 26:15:148. doi: 10.1186/s12876-015-0379-y.

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.

MeSH terms

  • Adenocarcinoma / enzymology*
  • Adenocarcinoma / genetics*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Aged
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / 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*
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / pathology
  • Repressor Proteins / metabolism

Substances

  • 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