HVEM/BTLA Immune Checkpoint Expression in Development of Gastric Cancer

Abstract Purpose: Regarding the role of B- and T-lymphocyte attenuator/Herpesvirus entry mediator (BTLA/HVEM) in tumorigenesis, this research was conducted to determine the HVEM/BTLA expression in development of gastric cancer.Methods: The statistical population of this study consisted of 114 patients, who were divided into 3 groups of non-ulcer dyspepsia (NUD; n=32), intestinal metaplasia (IM; n=19), and gastric cancer (GC; n=63). BTLA and HVEM in gastric biopsies were evaluated using SYBR Green-based on real-time PCR and immunohistochemistry. In this research, soluble HVEM (sHVEM) concentration and anti-Helicobacter pylori IgG antibody were assessed in sera of all study subjects. Results: Our result showed that in contrast to mRNA, HVEM protein expression was significantly higher in the GC group, compared to that in the NUD and IM groups (P<0.0001 and P=0.0002, respectively). It was found that BTLA mRNA expression was significantly higher in the GC group than in the IM and NUD groups (P=0.004 and P=0.0003, respectively). It was also significantly elevated in the advanced stages of GC (P=0.039). IHC results showed significant expression of BTLA in GC and IM groups, compared to the NUD group (P=0.0002, and P=0.008, respectively), and advanced stages than early stages of gastric cancer (p = 0.005). The sHVEM concentration was also higher in the GC group than in the NUD groups (P=0.001). Conclusions: High expression of BTLA/HVEM and sHVEM suggested that this inhibitory pathway is involved in immune regulation and progression of IM and GC. Therefore, these molecules can be used for the diagnosis and prognosis of GC.