DKK2 Impairs Tumor Immunity Infiltration and Correlates with Poor Prognosis in Pancreatic Ductal Adenocarcinoma
DKK2 Impairs Tumor Immunity Infiltration and Correlates with Poor Prognosis in Pancreatic Ductal Adenocarcinoma
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DKK2 损害肿瘤免疫浸润并与胰腺导管腺癌的不良预后相关
DOI：
10.1155/2019/8656282
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发表时间：
2019-09-08
影响因子：
4.1
通讯作者：
Sun, Yongwei
中科院分区：
文献类型：
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作者：
Yang, Jianyu;Jiang, Yongsheng;Sun, Yongwei
胰腺导管腺癌（PDAC）仍然是最具破坏性的癌症类型之一，尽管现代医学的进步。在我们目前的研究中，我们发现dickkopf相关蛋白2（DKK 2）在PDAC中的表达高于组织芯片中相邻胰腺组织。此外，DKK 2的高表达预示患者的预后较差，并且与肿瘤分化不良呈正相关。多因素考克斯回归分析证实DKK 2表达是PDAC的独立预后因素。基于基因集富集分析（GSEA），DKK 2的高表达与细胞迁移和上皮间质转化相关，而PDAC细胞中DKK 2的敲低导致细胞迁移受损。此外，GSEA预测肿瘤免疫侵袭与DKK 2表达呈负相关。然后，我们证实了这些结果，并证明了DKK 2的更高表达赋予了CD8+ T细胞的募集。我们的工作表明，DKK 2赋予肿瘤免疫逃避，并与胰腺导管腺癌的预后不良有关。
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.