Expression of Toll-like receptors in oral squamous cell carcinoma

PLoS One. 2024 Apr 9;19(4):e0300437. doi: 10.1371/journal.pone.0300437. eCollection 2024.

Abstract

Almost 380,000 new cases of oral cancer were reported worldwide in 2020. Oral squamous cell carcinoma (OSCC) accounts for 90% of all types of oral cancers. Emerging studies have shown association of Toll-like receptors (TLRs) in carcinogenesis. The present study aimed to investigate the expression levels and tissue localization of TRL1 to TRL10 and NF-κB between OSCC and healthy oral mucosa, as well as effect of Candida colonization in TRL expression in OSCC. Full thickness biopsies and microbial samples from 30 newly diagnosed primary OSCC patients and 26 health controls were collected. The expression of TLR1 to TLR10 and NF-κB was analyzed by immunohistochemistry. Microbial samples were collected from oral mucosa to detect Candida. OSCC epithelium showed lower staining intensity of TRL1, TRL2 TRL5, and TRL8 as compared to healthy controls. Similarly, staining intensity of TRL3, TRL4, TRL7, and TRL8 were significantly decreased in basement membrane (BM) zone. Likewise, OSCC endothelium showed lower staining intensity of TLR4, TLR7 and TLR8. Expression of NF-κB was significantly stronger in normal healthy tissue compared to OSCC sample. Positive correlation was found between the expression of NF-κB, TRL9 and TRL10 in basal layer of the infiltrative zone OSCC samples (P = 0.04 and P = 0.002, respectively). Significant increase in TRL4 was seen in BM zone of sample colonized with Candida (P = 0.01). According to the limited number of samples, our data indicates downregulation of TLRs and NF-κB in OSCC, and upregulation of TLR4 expression with presence of Candida.

MeSH terms

  • Carcinoma, Squamous Cell* / pathology
  • Head and Neck Neoplasms*
  • Humans
  • Mouth Neoplasms* / pathology
  • NF-kappa B / metabolism
  • Squamous Cell Carcinoma of Head and Neck
  • Toll-Like Receptor 4 / metabolism
  • Toll-Like Receptors

Substances

  • NF-kappa B
  • Toll-Like Receptor 4
  • Toll-Like Receptors

Grants and funding

This work was supported by the Suomen Hammaslääkäriseura Apollonia (Finnish Dental Society Apollonia) and the Helsingin ja Uudenmaan Sairaanhoitopiiri (Helsinki University Central Hospital) Research Funds. JR was supported by Academy of Finland. RR-R was supported by NIHR Manchester Biomedical Research Centre. The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript.