Abstract
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most devastating cancer types despite the improvement of modern medicine. In our present study, we found that dickkopf-related protein 2 (DKK2) shares a higher expression in PDAC compared with adjacent pancreas tissue in tissue microarray. In addition, an elevated expression of DKK2 predicts poorer prognosis of patients and positively correlated with poor tumor differentiation. Multivariate Cox regression analysis was also performed and confirmed that the expression of DKK2 is an independent prognostic factor in PDAC. A high expression of DKK2 correlates with cell migration and epithelial mesenchymal transition based on gene set enrichment analysis (GSEA) while knockdown of DKK2 in PDAC cells resulted in impaired cellular migration. Furthermore, GSEA predicts negative correlation between tumor immunity invasion and DKK2 expression. We then confirmed these results and demonstrated that a higher expression of DKK2 imparts the recruitment of CD8+ T cells. Our work suggested that DKK2 imparts tumor immune evasion and is associated with poor prognosis in pancreatic ductal adenocarcinoma.
Highlights
Pancreatic ductal adenocarcinoma (PDAC) is the sixth leading cause of cancer-related deaths in China and the fourth in Western countries [1, 2]
The expression of dickkopf-related protein 2 (DKK2) in PDAC is the highest among almost all kinds of cancer types based on The Cancer Genome Atlas (TCGA) data (Figure 1(c))
We found that the mRNA expression level of DKK2 in tumor tissue is higher than that in adjacent tissue especially in PDAC, which suggested that DKK2 is remarkably upregulated in PDAC tissue
Summary
Pancreatic ductal adenocarcinoma (PDAC) is the sixth leading cause of cancer-related deaths in China and the fourth in Western countries [1, 2]. The death rates of most cancer have decreased due to improvements in early detection and treatment, the overall 5-year survival of pancreatic ductal adenocarcinoma patients has increased only slightly from 3% to 5%, on account of the early and aggressive local invasion and metastatic potential [4]. Surgery is the most effective curative option for PDAC patients, but only 20% are suitable for resection, and only around 2025% of those survive to 5 years [5, 6]. A hotspot in studying PDAC is identification of more prognostic indicators and biological markers. The prognostic values of altered genes/proteins involved in tumorigenesis and progression of PDAC, such as P53, CDKN2A, and DPC4 [10], were more and more explored
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