KDM4D Predicts Recurrence in Exocrine Pancreatic Cells of Resection Margins from Patients with Pancreatic Adenocarcinoma

Anticancer Res. 2018 Apr;38(4):2295-2302. doi: 10.21873/anticanres.12474.


Background/aim: The role of histone demethylators, such as Jumonji domain 2 (JMJD2/KDM4) proteins, and histone deacetylases, such as sirtuins (SIRT) is poorly characterized in pancreatic carcinomas while they have a major role in the carcinogenesis of several other tumours.

Materials and methods: We assessed retrospectively with immunohistochemistry the expressions of KDM4A, KDM4B and KDM4D in 81 and SIRT1-4 in 102 pancreatic adenocarcinomas. Immunostaining was evaluated separately in benign pancreatic tissues and in malignant cells.

Results: High nuclear KDM4D expression in benign pancreatic tissue from resection margins associated with dismal disease-free survival (DFS) (OR=8.00; 95%CI=1.87-33.9; p=0.005), even more significantly than tumour size and lymph node involvement. High cytoplasmic SIRT2 expression in benign pancreatic tissues also associated with a shorter DFS, but only in univariate analysis (p=0.026).

Conclusion: Nuclear KDM4D and SIRT2 expression deviated from that of benign pancreatic tissue thus putatively influencing gene expression of tumor cells. Regardless, none of the enzymes studied had a decisive role in the spread of pancreatic cancer. A high nuclear expression of KDM4D in samples of pancreatic resection margins significantly and independently predicted an earlier recurrence and could thus be used in the assessment of risk of relapse in clinical practice.

Keywords: Epigenetics; KDM4; immunohistochemistry; pancreatic cancer; sirtuin.

MeSH terms

  • Adenocarcinoma / diagnosis*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Adenocarcinoma / surgery
  • Biomarkers, Tumor / metabolism
  • Cell Nucleus / metabolism
  • Cell Nucleus / pathology
  • Disease-Free Survival
  • Follow-Up Studies
  • Humans
  • Immunohistochemistry
  • Jumonji Domain-Containing Histone Demethylases / metabolism*
  • Margins of Excision*
  • Neoplasm Recurrence, Local / diagnosis*
  • Neoplasm Recurrence, Local / metabolism
  • Pancreas, Exocrine / metabolism
  • Pancreas, Exocrine / pathology
  • Pancreas, Exocrine / surgery*
  • Pancreatic Neoplasms / diagnosis*
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology
  • Pancreatic Neoplasms / surgery
  • Prognosis
  • Retrospective Studies
  • Sirtuin 2 / metabolism


  • Biomarkers, Tumor
  • Jumonji Domain-Containing Histone Demethylases
  • KDM4D protein, human
  • SIRT2 protein, human
  • Sirtuin 2