DKK2 Impairs Tumor Immunity Infiltration and Correlates with Poor Prognosis in Pancreatic Ductal Adenocarcinoma

Author:

Yang Jianyu1,Jiang Yongsheng1,He Ruizhe1,Liu Wei1,Yang Minwei1,Tao Lingye1,Fu Xueliang1,Shen Yang1,Li Jiao2,Liu Dejun1,Huo Yanmiao1,Zhang Junfeng1,Hua Rong1ORCID,Zhang Zhigang3ORCID,Sun Yongwei1ORCID

Affiliation:

1. Department of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

2. Department of Hepatobiliary Pancreas Surgery, Shanghai East Hospital, Tong Ji University School of Medicine, Shanghai, China

3. State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

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.

Funder

National Natural Science Foundation of China

Publisher

Hindawi Limited

Subject

Immunology,General Medicine,Immunology and Allergy

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