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

Asian Pac J Cancer Prev. 2024 Aug 1;25(8):2669-2677. doi: 10.31557/APJCP.2024.25.8.2669.

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.

MeSH terms

  • Adult
  • Aged
  • Antigens, CD* / genetics
  • Antigens, CD* / metabolism
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Case-Control Studies
  • Clinical Relevance
  • Dyspepsia* / genetics
  • Dyspepsia* / metabolism
  • Dyspepsia* / pathology
  • Female
  • Follow-Up Studies
  • GPI-Linked Proteins* / genetics
  • GPI-Linked Proteins* / metabolism
  • Humans
  • Male
  • Middle Aged
  • Peptic Ulcer* / genetics
  • Peptic Ulcer* / metabolism
  • Peptic Ulcer* / pathology
  • Prognosis
  • RNA, Messenger / genetics
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism
  • Stomach Neoplasms* / genetics
  • Stomach Neoplasms* / metabolism
  • Stomach Neoplasms* / pathology
  • Tumor Necrosis Factor Ligand Superfamily Member 14* / genetics
  • Tumor Necrosis Factor Ligand Superfamily Member 14* / metabolism

Substances

  • Tumor Necrosis Factor Ligand Superfamily Member 14
  • TNFSF14 protein, human
  • Antigens, CD
  • GPI-Linked Proteins
  • CD160 protein, human
  • Biomarkers, Tumor
  • Receptors, Immunologic
  • RNA, Messenger