The role of toll-like receptors (TLRs) in pan-cancer

Ann Med. 2022 Dec;54(1):1918-1937. doi: 10.1080/07853890.2022.2095664.

Abstract

Background: Toll-like receptors (TLRs) are important components of the innate and adaptive immune systems, and abnormal TLR expression has been linked to a variety of cancers. However, there was a lack of clarity on the association of TLR stimulation with the carcinogenesis of cancer. The study's goal was to analyse the clinical importance of TLRs expression at the mRNA level in pan-cancer datasets, as well as the link between TLR expression and carcinogenesis, progression, and clinical prognosis.

Methods: The expression profile of TLRs derived from UCSC pan-cancer data was analysed in multiple dimensions, including clinical analysis, immunological subtype analysis, tumour microenvironment (TME) analysis, tumour stem cell correlation analysis, and drug sensitivity analysis. Additionally, we analyse protein-protein interactions, functional enrichment, and chromatin accessibility, as well as TLR expression in single-cell sequencing data.

Results: Our multi-omics analysis results imply that TLRs may operate as a biological marker for carcinogenesis and progression, a potential target for anti-tumour therapy, and a prognostic biomarker, laying the theoretical groundwork for future translational medicine research.

Conclusion: TLRs are involved in the formation of malignancies and can be explored in further detail as potential prognostic indicators. Key MessagesToll-like receptors (TLRs) are key factors in the process of the innate and adaptive immune response, and their aberrant expression of TLRs have been widely reported in various cancer. However, the association between TLRs stimulation and tumorigenesis of cancer has not been well clarified.In this study, in the pan-cancer data, integrated TLR family gene expression analysis, clinical correlation analysis, immune subtype correlation analysis, tumour microenvironment correlation analysis, tumour stem cell correlation analysis, and drug sensitivity correlation analysis were performed.TLRs play an important role in the development of tumours and can be studied in depth as potential prognostic markers.

Keywords: Toll-like receptors (TLRs); data-mining; multi-omics; pan-cancer; tumour microenvironment (TME).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinogenesis
  • Humans
  • Neoplasms* / genetics
  • Prognosis
  • Toll-Like Receptors* / genetics
  • Toll-Like Receptors* / metabolism
  • Tumor Microenvironment / genetics

Substances

  • Toll-Like Receptors

Grants and funding

This study was supported in part by the National Natural Science Foundation of China (Grant No. 81702659; 81772856; 82073207; 82002923; 82173168); National Natural Science Foundation of China, joint fund cultivation project (Grant No. U1504822); Shanghai Rising-Star Program (No. 21QA1407500); Youth Fund of Shanghai Municipal Health Planning Commission (No. 2017YQ054; 2017Y0117); Interdisciplinary Program of Shanghai Jiao Tong University (No. YG2017MS26); Shanghai Talent Development Fund (No. 2018094); Henan medical science and technology research project (No. 201602031); Henan Medical Science and technology research plan, joint project of the Ministry and the province, (No. SB201901037); Henan Provincial Department of science and technology, social development project (No. 142102310055). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.