High expression of interleukin-22 and its receptor predicts poor prognosis in pancreatic ductal adenocarcinoma

摘要

Background: The cytokine interleukin-22 (IL-22) and its receptor are present in the tumor microenvironment. Their function in pancreatic ductal adenocarcinoma (PDAC) remains largely unknown. The goal of the present study was to measure the expression of IL-22 and IL-22R in PDAC and assess their relationship with clinicopathological features and prognosis. Methods: The expression of IL-22 and IL-22R was evaluated by immunohistochemistry in PDAC tissues from 57 patients and by Western blotting in six tumors and adjacent nontumor tissues. A statistical analysis was conducted to assess the relationship between levels of expression, clinicopathological factors, and overall survival. In addition, the relationship between the expression of IL-22 and IL-22R and invasion was assessed by Western blotting and transwell assay with the PDAC cell lines PANC1 and BxPC3. Results: Positive IL-22 staining was detected in PDAC tissues and adjacent nontumor tissues. Positive IL-22R staining was detected in PDAC cells. High expression of IL-22 and IL-22R correlated significantly with lymph node involvement. IL-22 increased the phosphorylation of signal transducer and activator of transcription3, the expression of matrix metalloproteinase 9, and the invasion in PANC1 and BxPC3 cells in vitro while silencing of IL-22R RNA caused opposite effects. Most importantly, overall survival was significantly poorer in patients with high expression of IL-22 and IL-22R than in those with low expression. Conclusions: These findings reveal the positive role of IL-22 and IL-22R in invasion and metastasis in human PDAC. IL-22 and IL-22R may be suitable independent prognostic markers in PDAC.