High expression of HVEM is associated with improved prognosis in intrahepatic cholangiocarcinoma

Ma,Bingqi; Meng,Huijuan; Tian,Ye; Wang,Yingying; Song,Tianqiang; Zhang,Ti; Wu,Qiang; Cui,Yunlong; Li,Huikai; Zhang,Wei; Li,Qiang

doi:10.3892/ol.2020.12330

High expression of HVEM is associated with improved prognosis in intrahepatic cholangiocarcinoma

Authors:
- Bingqi Ma
- Huijuan Meng
- Ye Tian
- Yingying Wang
- Tianqiang Song
- Ti Zhang
- Qiang Wu
- Yunlong Cui
- Huikai Li
- Wei Zhang
- Qiang Li
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Affiliations: Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital; National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin's Clinical Research Center for Cancer, Tianjin 300060, P.R. China, Affiliated Hospital of Weifang Medical University, Weifang, Shandong 261031, P.R. China, Department of Senior Ward, Tianjin Medical University Cancer Institute and Hospital; National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin's Clinical Research Center for Cancer, Tianjin 300060, P.R. China
Published online on: November 25, 2020 https://doi.org/10.3892/ol.2020.12330
Article Number: 69
Copyright: © Ma et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Herpesvirus entry mediator (HVEM) displays dual signals in T‑cell activation according to the ligands and intracytoplasmic effectors it interacts with. High HVEM expression may play an immunosuppressive role in several malignancies. The present study investigated the clinical impact of HVEM on intrahepatic cholangiocarcinoma (ICC), including its prognostic value, and association with clinicopathological features and immune status. The clinical data of 102 consecutive patients with ICC who underwent surgical treatment from January 2012 to December 2017 were collected. The expression of HVEM and different types of tumor‑infiltrating lymphocytes (TILs) were investigated in ICC tissue samples by immunohistochemical staining. HVEM expression was detected in the tumor tissues of 92 (90.2%) patients with ICC. Patients with high HVEM expression were more likely to have increased peripheral blood lymphocyte (PBL) concentrations (P=0.031), decreased CEA (P=0.036), low TNM stage (P=0.043) and high frequencies of small‑duct histological type (P=0.021) and BAP1 retained expression (P=0.010). Survival analysis showed that high HVEM expression was a favorable independent predictor of overall postoperative survival (P=0.034, hazard ratio=0.486, 95% confidence interval=0.249‑0.945). In addition, no significant association of HVEM expression with CD4+ (P=0.512), CD8+ (P=0.750) or CD45RO+ (P=0.078) TILs was identified in the ICC tissues. These results indicate that HVEM may serve as a favorable prognostic marker for ICC. Furthermore, co‑stimulatory signals from HVEM may play a dominant role in the progression of ICCs, which can be explained by an increase in the number of PBLs rather than a change in the number of TILs. However, the function of the HVEM network in ICC progression is complex and requires further study.

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