Toll-like receptors 1, 2, 4, 5, and 6 in gastric cancer

• Published in: Virchows Archiv : an international journal of pathology 2024-10, Vol.485 (4), p.655-664
• Main Authors: Eskuri, Maarit, Kemi, Niko, Helminen, Olli, Huhta, Heikki, Kauppila, Joonas H
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Biomarkers; Biomarkers, Tumor - analysis; Biomarkers, Tumor - metabolism; Cancer; Female; Gastric cancer; Histology; Humans; Immune system; Immunohistochemistry; Intestine; Kaplan-Meier Estimate; Male; Medicin och hälsovetenskap; Medicine; Medicine & Public Health; Middle Aged; Multivariate analysis; Original Article; Pathology; Prognosis; Proteins; Stomach Neoplasms - metabolism; Stomach Neoplasms - mortality; Stomach Neoplasms - pathology; Subgroups; Survival; Tissue Array Analysis; TLR1 protein; TLR2 protein; TLR4 protein; TLR5 protein; Toll-Like Receptor 1 - analysis; Toll-Like Receptor 1 - metabolism; Toll-Like Receptor 2 - analysis; Toll-Like Receptor 2 - metabolism; Toll-Like Receptor 4 - analysis; Toll-Like Receptor 4 - metabolism; Toll-Like Receptor 5 - analysis; Toll-Like Receptor 5 - metabolism; Toll-Like Receptor 6 - analysis; Toll-Like Receptor 6 - metabolism; Toll-like receptors; Toll-Like Receptors - analysis; Toll-Like Receptors - metabolism; Tumor cells; Tumors
• ISSN: 0945-6317; 1432-2307; 1432-2307
• DOI: 10.1007/s00428-023-03635-1

Toll-like receptors (TLRs) are expressed on both immune cells and tumor cells, triggering both anti-tumor and pro-tumor responses. Therefore, TLRs have potential as prognostic biomarkers and immunotherapeutic targets. The aim of this study was to investigate TLR1, TLR2, TLR4, TLR5, and TLR6 expression and association with clinicopathological variables and survival in gastric cancer. Immunohistochemical study on cancer specimens from 564 resected gastric cancer patients was performed using tissue microarrays. The association between patient survival and TLR expression was calculated with Cox regression adjusted for confounding factors. Patients with high cytoplasmic TLR2 expression had significantly poorer 5-year survival than the low cytoplasmic TLR2 expression group in multivariate analysis (adjusted HR 1.38, 95% CI 1.11–1.71), and this estimate was similar in intestinal type (adjusted HR 1.33, 95% CI 0.98–1.80) and diffuse type (adjusted HR 1.48, 95% CI 1.06–2.05) histology subgroups. Patients with high cytoplasmic TLR6 expression group had significantly better 5-year survival compared with low cytoplasmic TLR6 expression group in multivariate analysis (adjusted HR 0.74, 95% CI 0.60–0.91). In the subgroup analysis of diffuse type of histology, the 5-year survival was better in high cytoplasmic TLR6 expression group in multivariable analysis (HR 0.62, 95% CI 0.46–0.83). In the intestinal type of histology subgroup, no significant differences between the groups were present. TLR1, TLR4, and TLR5 expression were not associated with 5-year survival. In conclusion, cytoplasmic TLR2 and TLR6 expression seem to have independent prognostic impact in gastric cancer, while TLR1, TLR4, and TLR5 do not.