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Increased BTLA and HVEM in gastric cancer are associated with progression and poor prognosis

Authors Lan X, Li S, Gao H, Nanding A, Quan L, Yang C, Ding S, Xue Y

Received 29 November 2016

Accepted for publication 5 January 2017

Published 16 February 2017 Volume 2017:10 Pages 919—926


Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Ru Chen

Peer reviewer comments 2

Editor who approved publication: Dr Ingrid Espinoza

Xiuwen Lan,1,* Sen Li,1,* Hongyu Gao,1 Abiyasi Nanding,2 Lina Quan,3 Chunyan Yang,4 Shaohua Ding,2 Yingwei Xue1

1Department of Gastroenterological Surgery, 2Department of Pathology, 3Department of Hematology, The Affiliated Tumor Hospital, 4Department of Epidemiology and Biostatistic, Public Health School, Harbin Medical University, Harbin, People’s Republic of China

*These authors contributed equally to this work

Purpose: Deregulation of immune checkpoint molecules by tumor cells is related to immune escape. This study was conducted to investigate the relationship between the appearance of B- and T-lymphocyte attenuator (BTLA) and its ligand herpesvirus entry mediator (HVEM) with the prognosis in gastric cancer patients.
Patients and methods: A total of 136 patients with curative gastrectomy were included. The expression of BTLA and HVEM was detected by immunohistochemistry, and its correlation with the clinical significance of gastric cancer was further analyzed.
Results: The positivity of BTLA and HVEM was detected in 74.3% (101/136) and 89.0% (121/136) of the gastric cancer specimens, respectively. A high expression of BTLA and HVEM was detected, respectively, in 28.7% (39/136) and 44.9% (61/136) of the specimens. Characteristics analysis showed that the high expression of BTLA was significantly associated with lymph node metastasis (P=0.030). Similarly, the high expression of HVEM was also significantly correlated with lymph node metastasis (P=0.007) and depth of invasion (P=0.011). In addition, there was a positive correlation between the expression of BTLA and HVEM in gastric cancer specimens (r=0.245, P=0.004). Univariate analysis revealed that the high expression of BTLA and HVEM was associated with overall survival of patients along with tumor size, Borrmann type, depth of invasion, lymph node metastasis, and histological grade (P<0.05). Multivariate analysis established that the high expression of HVEM (P=0.010), depth of invasion (P=0.001), lymph node metastasis (P<0.001), and histological grade (P=0.027) were independent prognostic factors associated with overall survival in patients with gastric cancer.
Conclusion: The increased BTLA and HVEM levels correlate with the development and poor prognosis of gastric cancer. HVEM is an important prognostic indicator, and BTLA/HVEM pathway is considered to be a promising candidate for immunotherapy of gastric cancer.

gastric cancer, B- and T-lymphocyte attenuator, herpesvirus entry mediator, prognostic

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