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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.
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1 The Catholic University of Korea, Division of Oncology, Department of Internal Medicine, College of Medicine, Seoul, Republic of Korea (GRID:grid.411947.e) (ISNI:0000 0004 0470 4224)
2 The Catholic University of Korea, Cancer Research Institute, College of Medicine, Seoul, Republic of Korea (GRID:grid.411947.e) (ISNI:0000 0004 0470 4224)
3 The Catholic University of Korea, Department of Hospital Pathology, Uijeongbu St. Mary’s Hospital, College of Medicine, Seoul, Republic of Korea (GRID:grid.411947.e) (ISNI:0000 0004 0470 4224)
4 Chung-Ang University, Department of Pathology, College of Medicine, Seoul, Republic of Korea (GRID:grid.254224.7) (ISNI:0000 0001 0789 9563)
5 The Catholic University of Korea, Uijeongbu St. Mary’s Hospital Clinical Research Laboratory, Seoul, Republic of Korea (GRID:grid.411947.e) (ISNI:0000 0004 0470 4224)
6 The Catholic University of Korea, Department of Surgery, Uijeongbu St. Mary’s Hospital, College of Medicine, Seoul, Republic of Korea (GRID:grid.411947.e) (ISNI:0000 0004 0470 4224)
7 The Catholic University of Korea, Division of Oncology, Department of Internal Medicine, College of Medicine, Seoul, Republic of Korea (GRID:grid.411947.e) (ISNI:0000 0004 0470 4224); The Catholic University of Korea, Cancer Research Institute, College of Medicine, Seoul, Republic of Korea (GRID:grid.411947.e) (ISNI:0000 0004 0470 4224)