Abstract

The role of β-catenin and Dickkopf-1 (DKK1) is dependent on the specific immunobiology of T cell inflammation in biliary tract cancer (BTC). We aimed to analyze the role of DKK1 or β-catenin as a prognostic factor in BTC, and determine the clinical associations of ß-catenin and DKK1 with CD8+ tumor-infiltrating lymphocytes (TIL). We used data from The Cancer Genome Atlas Research Network and the clinicopathological data of 145 patients with BTC who had undergone primary radical resection between 2006 and 2016. CD8+ TIL expression was a significant predictor of favorable overall survival (OS) and relapse-free survival (RFS) (median OS, 34.9 months in high-TIL, 16.7 months in low-TIL, P < 0.0001 respectively; median RFS, 27.1 months in high-TIL, 10.0 months in low-TIL, P < 0.0001 respectively). In the high-CD8+ TIL BTC group, the tumor expression of β-catenin and DKK1 had a significant negative impact on either OS or RFS. In the low-TIL BTC group, there were no differences according to ß-catenin and DKK1 expression. Cox regression multivariate analysis demonstrated that CD8+ TIL and β-catenin retained significant association with OS. Among patients with resected BTC, the β-catenin and DKK1 protein and high CD8+ TIL levels were associated with poor and good clinical outcomes, respectively.

Highlights

  • The role of β-catenin and Dickkopf-1 (DKK1) is dependent on the specific immunobiology of T cell inflammation in biliary tract cancer (BTC)

  • It is associated with high expression of matrix metalloproteinase 9 proteins, which play a role in tumor cell invasion, angiogenesis, and lymph node metastasis in BTC and are correlated with poor ­prognosis[15,16,18]

  • Research Network to identify the associations of Wnt/β-catenin gene expression in CD8 cells and clinical outcomes in BTC. mRNA expression data and clinical data were downloaded from the The Cancer Genome Atlas (TCGA) data portal

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Summary

Introduction

The role of β-catenin and Dickkopf-1 (DKK1) is dependent on the specific immunobiology of T cell inflammation in biliary tract cancer (BTC). In the high-CD8+ TIL BTC group, the tumor expression of β-catenin and DKK1 had a significant negative impact on either OS or RFS. Among patients with resected BTC, the β-catenin and DKK1 protein and high CD8+ TIL levels were associated with poor and good clinical outcomes, respectively. Recent studies have suggested that high DKK1 expression in BTC is associated with immunosuppressive conditioning through myeloid-derived suppressor cells(MDSC) and tumor-associated m­ acrophages[17]. It is associated with high expression of matrix metalloproteinase 9 proteins, which play a role in tumor cell invasion, angiogenesis, and lymph node metastasis in BTC and are correlated with poor ­prognosis[15,16,18]

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