Page 58 - SDIR5 Abstract book 21 12 2021.

POSTER PRESENTATIONS

P18

The role of TLR4 in sporadic colorectal cancer displaying microsatellite instability
MSI and EMAST

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Kristina Vuković Đerfi , Sonja Marinović , Tanja Matijević Glavan , Anita Škrtić , Sanja Kapitanović
1 Department of Molecular Medicine, Rudjer Boskovic Institute, Zagreb, Croatia
2 Department of Clincal Pathology and Cytology, University Hospital Merkur, Zagreb, Croatia

Background: Sporadic colorectal cancer remains a significant health problem worldwide. Microsatellite
instability (MSI) is recognized as one of the three main pathways that drive sporadic CRC tumorigenesis and
is frequently associated with specific immune response and better prognosis in early-stage CRC. Another
form of microsatellite instability that affects tetranucleotide repeats – EMAST, seems to be involved in the
progression of sporadic CRC by modulating biological behavior of CRC towards metastasis and poor survival
in patients. Current evidence implicates pro-inflammatory environment as a major trigger for EMAST.
Inflammation in colon is frequently the result of prolonged immune response to dysbiosis where TLR4
receptor plays a major role as a regulator of intestinal homeostasis. Yet, aberrant TLR4 signaling might lead
to the induction of proliferative and anti-apoptotic pathways, contributing to the tumor development.
Material and Methods: Patients were stratified into groups according to MSI and EMAST status by VNTR
analysis. Tumors were further examined with regard to TLR4 mRNA expression by qPCR and the expression
of TLR4 protein by immunohistochemistry and western blot. Results: Analysis showed that EMAST was
present in majority of MSI-H sporadic CRC tumors. Compared to normal mucosae, tumor tissue showed
increased overall expression of TLR4 mRNA. TLR4 protein analysis revealed concordance with findings of
mRNA expression, whereas microsatellite-stable (MSS) CRC tumors showed significantly higher levels of
TLR4 protein than tumors with high microsatellite instability. Conclusion: Our findings suggest that TLR4 is
involved in development of sporadic CRC, but plays a more prominent role in sporadic CRCs with intact
mismatch-repair system.
Keywords: colorectal cancer, microsatellite instability, toll-like receptor 4
This study is supported by Croatian Science Foundation Grant IP-2016-06-1430.

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