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

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. I...

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Main Authors: Jianyu Yang, Yongsheng Jiang, Ruizhe He, Wei Liu, Minwei Yang, Lingye Tao, Xueliang Fu, Yang Shen, Jiao Li, Dejun Liu, Yanmiao Huo, Junfeng Zhang, Rong Hua, Zhigang Zhang, Yongwei Sun
Format: Article
Language:English
Published: Wiley 2019-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2019/8656282
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author Jianyu Yang
Yongsheng Jiang
Ruizhe He
Wei Liu
Minwei Yang
Lingye Tao
Xueliang Fu
Yang Shen
Jiao Li
Dejun Liu
Yanmiao Huo
Junfeng Zhang
Rong Hua
Zhigang Zhang
Yongwei Sun
author_facet Jianyu Yang
Yongsheng Jiang
Ruizhe He
Wei Liu
Minwei Yang
Lingye Tao
Xueliang Fu
Yang Shen
Jiao Li
Dejun Liu
Yanmiao Huo
Junfeng Zhang
Rong Hua
Zhigang Zhang
Yongwei Sun
author_sort Jianyu Yang
collection DOAJ
description 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.
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institution Kabale University
issn 2314-8861
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language English
publishDate 2019-01-01
publisher Wiley
record_format Article
series Journal of Immunology Research
spelling doaj-art-cd6564b3d2b9460bbc0744e603fe62602025-02-03T01:13:02ZengWileyJournal of Immunology Research2314-88612314-71562019-01-01201910.1155/2019/86562828656282DKK2 Impairs Tumor Immunity Infiltration and Correlates with Poor Prognosis in Pancreatic Ductal AdenocarcinomaJianyu Yang0Yongsheng Jiang1Ruizhe He2Wei Liu3Minwei Yang4Lingye Tao5Xueliang Fu6Yang Shen7Jiao Li8Dejun Liu9Yanmiao Huo10Junfeng Zhang11Rong Hua12Zhigang Zhang13Yongwei Sun14Department of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Hepatobiliary Pancreas Surgery, Shanghai East Hospital, Tong Ji University School of Medicine, Shanghai, ChinaDepartment of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaState Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaPancreatic 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.http://dx.doi.org/10.1155/2019/8656282
spellingShingle Jianyu Yang
Yongsheng Jiang
Ruizhe He
Wei Liu
Minwei Yang
Lingye Tao
Xueliang Fu
Yang Shen
Jiao Li
Dejun Liu
Yanmiao Huo
Junfeng Zhang
Rong Hua
Zhigang Zhang
Yongwei Sun
DKK2 Impairs Tumor Immunity Infiltration and Correlates with Poor Prognosis in Pancreatic Ductal Adenocarcinoma
Journal of Immunology Research
title DKK2 Impairs Tumor Immunity Infiltration and Correlates with Poor Prognosis in Pancreatic Ductal Adenocarcinoma
title_full DKK2 Impairs Tumor Immunity Infiltration and Correlates with Poor Prognosis in Pancreatic Ductal Adenocarcinoma
title_fullStr DKK2 Impairs Tumor Immunity Infiltration and Correlates with Poor Prognosis in Pancreatic Ductal Adenocarcinoma
title_full_unstemmed DKK2 Impairs Tumor Immunity Infiltration and Correlates with Poor Prognosis in Pancreatic Ductal Adenocarcinoma
title_short DKK2 Impairs Tumor Immunity Infiltration and Correlates with Poor Prognosis in Pancreatic Ductal Adenocarcinoma
title_sort dkk2 impairs tumor immunity infiltration and correlates with poor prognosis in pancreatic ductal adenocarcinoma
url http://dx.doi.org/10.1155/2019/8656282
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