Clinical Significance of TNFSF14/LIGHT and CD160 in Gastric Cancer and Peptic Ulcer Dyspepsia

Abstract

Background: Previous studies have reported the role of the Herpes Virus Entry Mediator (HVEM) in various cancer including gastric cancer. However, the expression level and clinical significance of CD160 and Tumor Necrosis Factor Ligand Superfamily Member 14 (TNFSF14) pathways in gastric cancer and gastric dyspepsia patients have remained unexplored.

Methods: The study involved the collection of gastric tissue biopsies from 42 patients with non-ulcerative dyspepsia (NUD) as the control group, 43 gastric cancer (GC) patients, and 48 patients with peptic-ulcerative dyspepsia (PUD). All the patients were endoscopically examined at Imam Khomeini Hospital in Sari, Mazandaran, Iran. The expression levels of TNFSF14 and CD160 mRNA were assessed using quantitative real-time PCR (qPCR) with the SYBR Green method. Statistical analysis was performed to investigate the potential association between the clinical and experimental data.

Results: Among the 133 gastric endoscopic biopsies examined, LIGHT exhibited a significant overexpression in GC patients (p-value < 0.01). Moreover, the expression of TNFSF14 was higher in GC patients with stages I and II (p-value<0.05). Furthermore, GC patients with TNM stages III+IV were accompanied by high expression levels of LIGHT (p-value < 0.01) as well as CD160 (p-value<0.05). The expression of CD160 was also higher in younger adults with PUD (p-value<0.05). Whereas TNFSF14 exhibited higher expression in older adults with GC (p-value<0.05). Furthermore, this research provided insights into the potential biological pathways and significant gene enrichment of TNFSF14 and CD160, suggesting the potential role of CD160 and TNFSF14 in the regulation of immune system in GC and PUD.

Conclusion: These findings suggest the possible role of LIGHT and CD160 expression in gastric cancer patients in immune dysregulation toward gastric cancer. Targeted immunotherapy that harnessing co-stimulatory molecules like LIGHT and CD160 could be a promising approach in the treatment of GC as well as potential GC tumor markers.

Keywords: CD160 antigen; Dyspepsia; Gastric cancer; Tumor Necrosis Factor Ligand Superfamily Member 14.

Figure 1

Expression profiles of CD160 and TNFSF14 (LIGHT). Quantitative PCR was used to measure the relative expression of CD160 in gastric cancer (GC), peptic ulcer dyspepsia (PUD), and non-ulcer dyspepsia (NUD) groups. Figure 1A shows the relative expression of CD160 in the experimental groups compared to the NUD group as a control. B. The relative expression of TNFSF14 (LIGHT) is presented among the three study groups, illustrated TNFSF14 (LIGHT) overexpression in tissue samples from GC patients compared to NUD. The graphs show the data with Mean ± SEM values, and statistical significance was considered at P. values <0.05.

Figure 2

Expression Levels of TNFSF14/LIGHT and CD160 in Gastric Cancer Patients with Different TNM Stages Compared to the NUD Control Group. (A) Expression levels of TNFSF14/LIGHT in gastric cancer patients with TNM stages I+II (early-stage), TNM stages III+IV (advanced-stage), and NUD control group. The Kruskal-Wallis test showed a significant difference in TNFSF14/LIGHT expression levels among the three groups (p < 0.01). Pairwise comparisons revealed significantly higher expression of TNFSF14/LIGHT in gastric cancer patients with TNM stages I+II compared to the NUD control group (p < 0.05) and in gastric cancer patients with TNM stages III+IV compared to the NUD control group (p < 0.01). (B) Expression levels of CD160 in gastric cancer patients with TNM stages III+IV (advanced-stage) and NUD control group. The Kruskal-Wallis test showed a significant difference in CD160 expression levels between the two groups (p < 0.05). Data are presented as mean ± standard deviation. Pairwise comparisons were performed using Dunn's test. **p<0.01, *p<0.05. NUD, non-ulcer dyspepsia.

Figure 3

Comparison of CD160 and TNFSF14 Differential Gene Expression Levels Across Age among Patients with Peptic Ulcerative Dyspepsia (PUD), and Gastric Cancer (GC). A. Box plots show the median gene expression levels with significant differences with a p-value < 0.05*. Significant differences in CD160 gene expression were found between PUD patients over and under or equal to the median age of 55 years (p-value < 0.05), with higher expression in the younger PUD group. B. Significant differences in TNFSF14 gene expression were found between GC patients over and under or equal to the median age of 71 years (p-value < 0.05*), with higher expression in the older GC group. No significant differences were found in other comparisons (data not shown).