The role of Dickkopf-1 as a potential prognostic marker in pancreatic ductal adenocarcinoma

Dickkopf-1 作为胰腺导管腺癌潜在预后标志物的作用

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作者:De-Jun Liu, Yue-Xia Xie, Xiao-Xing Liu, Yan-Miao Huo, Min-Wei Yang, Xue-Liang Fu, Wei Liu, Jian-Yu Yang, Jiao Li, Rong Hua, Pei-Feng Liu, Yong-Wei Sun, Jun-Feng Zhang

Abstract

Dickkopf-1(DKK-1), the downstream target of β-catenin/T-cell factor, participates in a negative feedback loop in the Wnt signaling and reported as an important biomarker in many tumors. In this study, we analyzed the expression of DKK-1 in pancreatic ductal adenocarcinoma (PDAC) patients at both mRNA and protein levels. We used real-time PCR to detect the expression of DKK-1 in 32 PDAC and paired adjacent non-tumor tissues, results suggested that the expression of DKK-1 was increased in PDAC tissues. We found the similar results in the analysis of 3 independent microarray data sets. Immunohistochemical staining of 311 pairs of PDAC tissues suggested that DKK-1 expression was significantly associated with T classification (P = 0.039) and lymph node metastasis (P = 0.035). Furthermore, Kaplan-Meier analysis for DKK-1 expression demonstrated that patients with higher DKK-1 level had shorter overall survival (OS) and relapse-free survival (RFS) time in Ren Ji cohort and online PDAC database at both mRNA and protein levels. Univariable and multivariable Cox regression analysis confirmed that DKK-1 as well as lymph node metastasis and histology were independent predictors of OS in patients with PDAC. This study demonstrated that DKK-1 may be a predictor for prognosis in PDAC patients.

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