title: Increased BTLA and HVEM in gastric cancer are associated with progression and poor prognosis.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Gastroenterological Surgery.
authors.forename: Xiuwen
authors.initials: X
authors.lastname: Lan
authors.affiliation: Department of Gastroenterological Surgery.
authors.forename: Sen
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Gastroenterological Surgery.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Gao
authors.affiliation: Department of Pathology.
authors.forename: Abiyasi
authors.initials: A
authors.lastname: Nanding
authors.affiliation: Department of Hematology, The Affiliated Tumor Hospital.
authors.forename: Lina
authors.initials: L
authors.lastname: Quan
authors.affiliation: Department of Epidemiology and Biostatistic, Public Health School, Harbin Medical University, Harbin, People's Republic of China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Pathology.
authors.forename: Shaohua
authors.initials: S
authors.lastname: Ding
authors.affiliation: Department of Gastroenterological Surgery.
authors.forename: Yingwei
authors.initials: Y
authors.lastname: Xue
keywords: B- and T-lymphocyte attenuator; gastric cancer; herpesvirus entry mediator; prognostic