PIM-1 contributes to the malignancy of pancreatic cancer and displays diagnostic and prognostic value

J Exp Clin Cancer Res. 2016 Sep 5;35(1):133. doi: 10.1186/s13046-016-0406-z.

Abstract

Background: The effects of PIM-1 on the progression of pancreatic cancer remain unclear, and the prognostic value of PIM-1 levels in tissues is controversial. Additionally, the expression levels and clinical value of PIM-1 in plasma have not been reported.

Methods: The effects of PIM-1 on biological behaviours were analysed. PIM-1 levels in tissues and plasma were detected, and the clinical value was evaluated.

Results: We found that PIM-1 knockdown in pancreatic cancer cells suppressed proliferation, induced cell cycle arrest, enhanced apoptosis, resensitized cells to gemcitabine and erlotinib treatment, and inhibited ABCG2 and EZH2 mRNA expression. Our results indicated that PIM-1 and the EGFR pathway formed a positive feedback loop. We also found that PIM-1 expression in pancreatic cancer tissues was significantly upregulated and that a high level of expression was negatively associated with prognosis (P = 0.025, hazard ratio [HR] =2.113, 95 % confidence interval: 1.046-4.266). Additionally, we found that plasma PIM-1 levels in patients with pancreatic cancer were significantly increased and could be used in the diagnosis of pancreatic cancer. High plasma PIM-1 expression was an independent adverse prognostic factor for pancreatic cancer (P = 0.037, HR = 1.87, 95 % CI: 1.04-3.35).

Conclusion: Our study suggests that PIM-1 contributes to malignancy and has diagnostic and prognostic value in pancreatic cancer.

Keywords: Biomarkers; Chemoresistance; PIM kinases; Pancreatic cancer; Targeted therapy.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 2 / genetics*
  • Cell Cycle Checkpoints
  • Cell Line, Tumor
  • Cell Proliferation
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / pharmacology
  • Enhancer of Zeste Homolog 2 Protein / genetics*
  • Erlotinib Hydrochloride / pharmacology
  • Female
  • Gemcitabine
  • Gene Knockdown Techniques
  • Humans
  • Male
  • Neoplasm Proteins / genetics*
  • Pancreatic Neoplasms / blood
  • Pancreatic Neoplasms / diagnosis*
  • Pancreatic Neoplasms / genetics
  • Prognosis
  • Proto-Oncogene Proteins c-pim-1 / blood*
  • Proto-Oncogene Proteins c-pim-1 / genetics*
  • Signal Transduction
  • Survival Analysis

Substances

  • ABCG2 protein, human
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • Neoplasm Proteins
  • Deoxycytidine
  • Erlotinib Hydrochloride
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein
  • PIM1 protein, human
  • Proto-Oncogene Proteins c-pim-1
  • Gemcitabine