Thesis defence in the University of Oulu

Doctoral Candidate

Master of Science Päivi Sirniö

Faculty and research unit

University of Oulu Graduate School, Faculty of Medicine, Cancer and translational medicine research unit

Field of study

Pathology

Date and time of the thesis defence

8.11.2019 12:00

Place of the thesis defence

Lecture hall F101, Aapistie 7

Topic of the dissertation

Determinants of systemic inflammation in colorectal cancer

Opponent

Professor Caj Haglund, University of Helsinki

Custos

Professor Markus Mäkinen, University of Oulu

Identification of serum markers associated with systemic inflammation in colorectal cancer patients

Inflammation is known to play a significant role in the development and progression of cancer. In colorectal cancer (CRC), local inflammation is associated with better survival. On the contrary, the activation of systemic inflammation is associated with worse prognosis.

This study aimed to identify blood biomarkers associated with systemic inflammation, as measured by the modified Glasgow Prognostic Score (mGPS), in colorectal cancer patients.

Blood keratin 18 levels were increased in CRC patients with systemic inflammation compared to those without systemic inflammation. As keratin 18 is a protein released from epithelial cell during cell death, cell injury and systemic inflammation seem to be linked in CRC. However, more research is needed to determine in which tissues cell death occurs.

Elevated matrix metalloproteinase 8 levels were also associated with systemic inflammation. Matrix metalloproteinases are enzymes that degrade the extracellular matrix and contribute to inflammatory processes and cancer progression.

Moreover, the results showed that blood metabolite levels are altered in CRC patients with systemic inflammation. The levels of apolipoprotein A1, a major protein component of HDL particle, were decreased. Of the studied amino acids, lowered levels of glutamine and histidine and increased levels of phenylalanine were found in patients with systemic inflammation. Decreased glutamine levels may reflect enhanced glutamine consumption and muscle wasting during systemic inflammation. Several of the identified markers also associated with patient survival.

These findings provide new insight into the underlying factors and possible effects of systemic inflammation in CRC.

 

Dissertation

Last updated: 1.11.2019