Clinical and Oncological Impact of the Toll-like Receptor-3 and -4 in Esophageal and Gastro-esophageal Junction Adenocarcinoma

Anticancer Res. 2023 Jul;43(7):3183-3191. doi: 10.21873/anticanres.16492.

Abstract

Background/aim: Esophageal and gastro-esophageal junction cancer is a major cause of cancer-related mortality, with poor prognosis. Toll-like receptors (TLRs) play a significant role in the innate immune system; their increased expression has been associated with esophageal adenocarcinoma. This study aimed to determine the association between TLR-3 and TLR-4 expression with clinical and oncological outcomes of patients that underwent esophagectomy for cancer.

Patients and methods: This is a retrospective analysis of prospectively collected data from consecutive patients within a 2-year period. Primary endpoints of the study were the assessment of the expression of TLR-3 and TLR-4 in primary tumors as well as in metastatic lymph nodes. Secondary endpoints were the correlation of TLR-3 and TLR-4 values with the clinical, pathological, and oncological outcomes.

Results: A significantly higher expression of TLR-3 and TLR-4 in primary tumors and metastatic-lymph nodes was observed. There was a significant association between TLR-3 expression and T-stage, as well as TLR-4 expression and grade of differentiation in the primary site. Additionally, metastatic-lymph node TLR-4 expression was significantly correlated with N-stage. A strong correlation between TLR-4 expression and overall or progression-free survival rates was detected.

Conclusion: This study found a significantly increased TLR expression in malignant tissue/metastatic lymph nodes, as well as a significant positive correlation between TLRs and worse clinical outcomes. TLRs have a pivotal role in the inflammation pathway in the esophagus and during esophageal carcinogenesis. This study highlights the need for further investigation into TLR-mediated signaling pathways and their potential role as diagnostic and therapeutic targets.

Keywords: Esophageal cancer; adenocarcinoma; esophagectomy; outcomes; prognosis; toll-like receptors.

MeSH terms

  • Adenocarcinoma* / pathology
  • Esophageal Neoplasms* / pathology
  • Esophagectomy
  • Esophagus / pathology
  • Humans
  • Lymph Node Excision
  • Lymphatic Metastasis
  • Retrospective Studies
  • Stomach Neoplasms* / surgery
  • Toll-Like Receptor 3
  • Toll-Like Receptor 4 / metabolism
  • Toll-Like Receptors

Substances

  • Toll-Like Receptor 3
  • Toll-Like Receptor 4
  • Toll-Like Receptors

Supplementary concepts

  • Adenocarcinoma Of Esophagus