Abstract
BackgroundThe 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.MethodsThe effects of PIM-1 on biological behaviours were analysed. PIM-1 levels in tissues and plasma were detected, and the clinical value was evaluated.ResultsWe 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).ConclusionOur study suggests that PIM-1 contributes to malignancy and has diagnostic and prognostic value in pancreatic cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-016-0406-z) contains supplementary material, which is available to authorized users.
Highlights
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
We found that PIM-1 expression levels in pancreatic ductal adenocarcinoma (PDAC) cells were significantly downregulated after PIM-1 siRNA transfection compared with those of the control group (Additional file 1: Figure S1), which indicated that PIM-1 levels were successfully downregulated by siRNA
We investigated the expression levels of the pancreatic cancer stem cell markers Adenosine triphosphate-binding cassette superfamily G member 2 (ABCG2) [12] and Enhancer of zeste homologue 2 (EZH2) [13] by qRT-PCR, and we found that ABCG2 and EZH2 mRNA expression levels were significantly decreased following siRNA-mediated knockdown of PIM-1 expression (Fig. 3)
Summary
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. The expression levels and clinical value of PIM-1 in plasma have not been reported. Pancreatic cancer is one of the most deadly malignancies, with an overall 5-year survival rate of 5 % [1]. One of the main reasons for its poor prognosis is that few patients are diagnosed at an early stage [1]; a lack of efficient treatments and resistance to chemotherapy drugs are additional reasons [2]. PIM kinases play pivotal roles in tumour progression and anti-cancer drug resistance [5]. The role of PIM-1 in pancreatic cancer has been investigated.
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