Expression profile of Toll‑like receptors in human breast cancer

Mol Med Rep. 2020 Feb;21(2):786-794. doi: 10.3892/mmr.2019.10853. Epub 2019 Nov 26.

Abstract

Toll‑like receptors (TLRs) are the most widely studied pattern recognition receptors. Mounting evidence suggests an important association between TLRs and the occurrence and development of breast cancer. Thus, targeting these receptors may be a potential strategy for breast cancer treatment. The current study analyzed the data of 1,215 patients with breast cancer obtained from The Cancer Genome Atlas (TCGA) database. It was observed that, in addition to TLR6, TLR7 and TLR8, the expression of the remaining TLRs in breast cancer tissues was lower than that in normal tissues. In addition, TLR3 and TLR9 displayed significantly different expression levels in ER‑/PR‑negative breast cancer compared with the control tissues, while TLR5 expression was significantly reduced in HER2‑enriched breast cancer. Furthermore, TLR10 exhibited lower expression levels in advanced stages of the disease as compared with that observed in earlier stages. Survival analysis revealed that the expression of TLR4 and TLR7 had a significant impact on survival, and higher expression levels suggested worse prognosis. Finally, the expression levels of TLR1, TLR2, TLR4, TLR5, TLR6 and TLR10 were correlated with those of the inflammatory cytokines interleukin‑1β and tumor necrosis factor‑α, while the expression levels of TLR3, TLR7, TLR8 and TLR9 were correlated with those of interferon‑β and C‑X‑C motif chemokine ligand 10. Taken together, the current study results suggest that TLR expression may serve as a biomarker of cancer pathogenesis and progression, and may provide new insights for the treatment of breast cancer through the regulation and targeting of TLRs.

Keywords: Toll-like receptors; breast cancer; survival; inflammatory cytokines; the cancer genome atlas.

MeSH terms

  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Cytokines / metabolism*
  • Databases, Genetic
  • Disease Progression
  • Female
  • Humans
  • Middle Aged
  • Receptor, ErbB-2 / metabolism
  • Toll-Like Receptor 1 / genetics
  • Toll-Like Receptor 1 / metabolism
  • Toll-Like Receptor 10 / genetics
  • Toll-Like Receptor 10 / 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 5 / genetics
  • Toll-Like Receptor 5 / metabolism
  • Toll-Like Receptor 6 / genetics
  • Toll-Like Receptor 6 / metabolism
  • Toll-Like Receptor 7 / genetics
  • Toll-Like Receptor 7 / metabolism
  • Toll-Like Receptor 8 / genetics
  • Toll-Like Receptor 8 / metabolism
  • Toll-Like Receptor 9 / genetics
  • Toll-Like Receptor 9 / metabolism
  • Toll-Like Receptors / genetics
  • Toll-Like Receptors / metabolism*
  • Transcriptome / genetics*
  • Triple Negative Breast Neoplasms / genetics
  • Triple Negative Breast Neoplasms / metabolism*
  • Tumor Microenvironment / genetics

Substances

  • Cytokines
  • TLR1 protein, human
  • TLR10 protein, human
  • TLR2 protein, human
  • TLR3 protein, human
  • TLR4 protein, human
  • TLR5 protein, human
  • TLR6 protein, human
  • TLR7 protein, human
  • TLR8 protein, human
  • TLR9 protein, human
  • Toll-Like Receptor 1
  • Toll-Like Receptor 10
  • Toll-Like Receptor 2
  • Toll-Like Receptor 3
  • Toll-Like Receptor 4
  • Toll-Like Receptor 5
  • Toll-Like Receptor 6
  • Toll-Like Receptor 7
  • Toll-Like Receptor 8
  • Toll-Like Receptor 9
  • Toll-Like Receptors
  • ERBB2 protein, human
  • Receptor, ErbB-2