Toll-like receptors 2 and 4 in colorectal cancer

Thesis event information

Date and time of the thesis defence

Place of the thesis defence

Oulu University Hospital, auditorium 1

Topic of the dissertation

Toll-like receptors 2 and 4 in colorectal cancer

Doctoral candidate

Licentiate of Medicine, M.D. Karoliina Paarnio

Faculty and unit

University of Oulu Graduate School, Faculty of Medicine, Research Unit of Surgery, Anesthesia and Intensive Care, Cancer and Translational Medicine Research Unit

Subject of study

medicine

Opponent

docent Marja Hyöty, Tampere University Hospital

Custos

professor (emeritus) Jyrki Mäkelä, University of Oulu

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Toll-like receptors 2 and 4 in colorectal cancer

Colorectal cancer (CRC) is the third most common cancer worldwide, and its incidence is increasing. Inflammation associates with the pathogenesis of cancer by several mechanisms. Toll-like receptors (TLRs) mediate and regulate the inflammatory response and their role in cancer progression has been established in many cancers.
This study aimed to clarify the roles of TLR2 and TLR4 and their significance in the development, progression, and prognosis of CRC in relation to inflammation in a series of 149 CRC patients operated in Oulu University Hospital (2006–2010).
We characterized the tissue expression in CRC tumors and serum levels of TLR2 and TLR4, and the associations of expression patterns with tumor features and the prognosis of cancer. We found downregulation of TLR4 and upregulation of TLR2 in CRC, and low expression of TLR4 in the invasive front of the tumor predicted poor prognosis and metastatic disease. Serum TLR2 levels were inversely associated with systemic inflammation in patients with CRC, and our findings suggested that serum TLR2 levels might depend more on normal colorectal mucosa contributions than on tumor tissue. Also, the mean serum TLR4 levels were lower in patients than in controls.
We also found that tumor necrosis in CRC associated with low TLR4 expression in carcinoma epithelium, and low TLR4 expression associated with systemic inflammation. Tumoral TLR2 expression did not correlate with necrosis from systemic inflammation, but low expression of TLR2 in normal mucosa was linked to indicators of systemic inflammation, supporting the concept that the normal colon mucosa may contribute to the regulation of systemic inflammation.
In conclusion, TLR2 and TLR4 showed divergent roles in CRC. TLR2 was upregulated and TLR4 downregulated in CRC. Downregulation of TLR4 was related to tumoral necrosis and adverse prognosis. High normal mucosa TLR2 expression associated with high serum TLR2 concentration and signs of lower systemic inflammation.
Last updated: 30.11.2022