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.

Abstract

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