Toll-like receptors TLR-2, TLR-4, TLR-7, and TLR-9 in tumor tissue and serum of the patients with esophageal squamous cell carcinoma and gastro-esophageal junction cancer

Adv Clin Exp Med. 2019 Apr;28(4):515-522. doi: 10.17219/acem/87012.

Abstract

Background: Stimulation of toll-like receptors (TLRs) has been linked to the development of esophageal and gastric cancers.

Objectives: The aim of the study was to evaluate the clinical significance of tissue expression and serum concentration of TLR-2, TLR-4, TLR-7 and TLR-9 in patients with esophageal squamous cell carcinoma and gastro-esophageal junction adenocarcinoma.

Material and methods: The study group consisted of 97 individuals: 32 with esophageal squamous cell carcinoma, 27 with gastro-esophageal junction cancer, and 38 ageand gender-matched controls. The mRNA expression and protein concentration of TLRs in tissues and sera were measured by reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) tests.

Results: In esophageal cancer patients, mRNA expressions of TLR-2, TLR-4 and TLR-7, and protein concentrations of all TLRs were significantly higher in tumor than in control tissue (p < 0.05). In esophageal cancer patients with lymph node metastasis, a tendency toward higher protein concentrations of tumor TLR-4 was observed. In gastro-esophageal junction adenocarcinoma subgroup, only the mRNA expression of TLR-7 and protein concentrations of TLR-4, TLR-7 and TLR-9 were significantly higher in tumors than in normal mucosa (p < 0.05). Protein concentration of TLR-9 was significantly higher in tumors of gastro-esophageal junction cancer with lymph node metastasis and depth of tumor invasion. Diagnostic potential of serum TLR-4 as a marker of gastro-esophageal junction cancer presence was reported.

Conclusions: We demonstrated differences in the expression patterns of TLRs between esophageal squamous cell carcinoma and adenocarcinoma of gastro-esophageal junction, and showed circulating TLR-4 to be a potential marker of gastro-esophageal junction cancer.

Keywords: biomarkers; gastro-esophageal cancer; toll-like receptors.

MeSH terms

  • Adult
  • Biomarkers, Tumor
  • Case-Control Studies
  • Enzyme-Linked Immunosorbent Assay
  • Esophageal Neoplasms / metabolism*
  • Esophageal Neoplasms / pathology
  • Esophageal Squamous Cell Carcinoma / metabolism*
  • Esophageal Squamous Cell Carcinoma / pathology
  • Female
  • Gene Expression
  • Humans
  • Male
  • Middle Aged
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Toll-Like Receptor 2 / genetics
  • Toll-Like Receptor 2 / metabolism*
  • Toll-Like Receptor 3 / genetics
  • Toll-Like Receptor 3 / metabolism*
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / metabolism*
  • Toll-Like Receptor 7 / genetics
  • Toll-Like Receptor 7 / metabolism*
  • Toll-Like Receptor 9 / genetics
  • Toll-Like Receptor 9 / metabolism*
  • Toll-Like Receptors / genetics
  • Toll-Like Receptors / metabolism

Substances

  • Biomarkers, Tumor
  • RNA, Messenger
  • TLR3 protein, human
  • TLR4 protein, human
  • TLR7 protein, human
  • TLR9 protein, human
  • Toll-Like Receptor 2
  • Toll-Like Receptor 3
  • Toll-Like Receptor 4
  • Toll-Like Receptor 7
  • Toll-Like Receptor 9
  • Toll-Like Receptors