Decreased expression of HDAC8 indicates poor prognosis in patients with intrahepatic cholangiocarcinoma

Hepatobiliary Pancreat Dis Int. 2019 Oct;18(5):464-470. doi: 10.1016/j.hbpd.2019.07.006. Epub 2019 Jul 24.

Abstract

Background: Intrahepatic cholangiocarcinoma (ICC) is a highly malignant primary tumor in the liver, and the rates of incidence and mortality are rapidly increasing globally. Histone deacetylase 8 (HDAC8) is a transcriptional regulator and is associated with tumorigenesis of several tumor types. This study aimed to evaluate the correlation between HDAC8 expression and clinicopathological parameters in ICC patients.

Methods: ICC tissues and corresponding nonmalignant bile duct tissues were obtained from 60 patients. HDAC8 and Ki-67 expression were evaluated by immunohistochemistry staining. HDAC8 expression and the clinicopathological features and prognosis of the patients were analyzed. The mRNA level of HDAC8 in ICC was further analyzed using data from The Cancer Genome Atlas (TCGA).

Results: The expression of HDAC8 were lower in ICC tissues (39/60, 65%) than in the corresponding nonmalignant bile duct tissues (54/60, 90%) (P = 0.001). Low HDAC8 expression in ICC was significantly associated with lymph node metastases (47.6% vs. 17.9%, P = 0.015). In addition, the positive cells rate of HDAC8 was statistically and negatively correlated with the Ki-67 index in ICC lesions (r = -0.7660, P < 0.001). Importantly, the overall survival rate and recurrence-free survival rate in ICC patients with low HDAC8 expression were lower than those with high HDAC8 expression (P = 0.008 and P = 0.011, respectively).

Conclusions: Decreased HDAC8 expression in ICC is related to poor prognosis, and HDAC8 may be an independent prognostic indicator of ICC patients after curative resection.

Keywords: HDAC8; Intrahepatic cholangiocarcinoma; Prognosis.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Bile Duct Neoplasms / genetics
  • Bile Duct Neoplasms / metabolism*
  • Bile Duct Neoplasms / pathology
  • Bile Ducts, Intrahepatic / metabolism*
  • Cholangiocarcinoma / genetics
  • Cholangiocarcinoma / metabolism*
  • Cholangiocarcinoma / secondary
  • Disease-Free Survival
  • Female
  • Histone Deacetylases / genetics*
  • Histone Deacetylases / metabolism*
  • Humans
  • Ki-67 Antigen / metabolism
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • RNA, Messenger / metabolism
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism*
  • Survival Rate

Substances

  • Ki-67 Antigen
  • RNA, Messenger
  • Repressor Proteins
  • HDAC8 protein, human
  • Histone Deacetylases