Page 43 - SDIR5 Abstract book 21 12 2021.

POSTER PRESENTATIONS

P3

Gene expression profiling of MSI and EMAST colorectal cancers

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Sonja Marinović , Kristina Vuković Đerfi , Anita Škrtić , Sanja Kapitanović
1 Department of Molecular Medicine, Ruđer Bošković Institute, Zagreb, Croatia
2 Department of Clinical Pathology and Cytology, University Hospital Merkur, Zagreb, Croatia

Background: Sporadic colorectal cancer (CRC) occurs via progressive accumulation of genetic alterations,
genomic instability, or deficiency in DNA mismatch repair (MMR). Even though etiology of both
microsatellite instability (MSI) and microsatellite alterations at selected tetranucleotide repeats (EMAST) is
due to DNA MMR deficiency, they represent distinct subset of CRCs. EMAST CRCs have been poorly studied,
however, they were linked to a chronic inflammation and overall poor prognosis. Contrarily, MSI CRCs have
been shown to represents a unique subset of CRC that is associated with high immune cell infiltration,
better prognoses, and good response to checkpoint inhibitors.
EMAST development has been brought into connection with overexpression of IL-6 and the dysfunction of
MSH3 whereas MSI development with loss of expression of MSH2 and MLH1. Therefore, we decided to
investigate mRNA expression of MMR genes and IL-6 as well as IL-1β as one of the most important
proinflammatory cytokines in tumorigenesis. Material and methods: CRC patients were divided into three
groups based on their MSI-H and/or EMAST-H status. From each group twenty samples of tumor and
normal adjacent tissues were taken and mRNA was isolated to evaluate the expression of MSH2, MLH1,
MSH3, IL-6 and IL-1β with real-time qPCR. Results: When different groups were compared analysis showed
that MLH1 expression was significantly reduced, and MSH2 and IL-1β significantly increased in MSI-H tumor
tissues compared to other groups. There were no differences in the expression of MSH3, and IL-6 between
different groups. Conclusions: Our findings confirmed already established role of MLH-1 in development of
MSI-H tumors. In addition, increased expression of MSH-2 and IL-1β suggests a role in MSI-H CRC
tumorigenesis.
This study is supported by Croatian Science Foundation Grant IP-2016-06-1430.

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