Ekspresjon av DNA-reparasjonsprotein PARP1 i ulcerøs kolitt og kolorektalkreft: En immunhistokjemisk studie

The cell's genomic integrity is essential for all life forms, and is constantly being exposed to both endogenous and exogenous threats. In order to preserve this integrity, through evolution, the cells have developed a toolbox of biomechanisms which collectively make up the cells’ DNA damage response. One of these mechanisms is DNA repair; consisting of an extensive network of repair proteins, specialized in repairing DNA damage. The daily amount of DNA damage induced in each cell can be as much as 105 lesions. Accumulation of DNA damage over time trigger genomic instability, which is a hallmark of cancer. Reactive oxygen and nitrogen species (RONS) are among the most common sources of DNA damage. Ulcerative colitis is an intestinal disease caused by chronic idiopathic inflammation, affecting the colon to a varying extent and degree. Oxidative and nitrative stress in chronic inflamed tissue promotes a tumor microenvironment that accelerates the increased production of RONS. As a result, the concentration of DNA damage is high in the colon epithelia of UC patients. It is believed that high concentrations of DNA damage are an important predisposing factor for the progression to colitis-associated colorectal cancer (CAC) in UC-patients. Unlike sporadic colorectal cancer (CRC), CAC is more frequent in younger individuals as progression from dysplastic UC to CAC may advance faster compared to the more prolonged progression of sporadic CRC. In a previous study, our research group has used immunohistochemistry, digital pathology, and semiquantitative cell counting to study the expression pattern of the NUCKS1 DNA double-strand break repair protein in colon biopsies from patients with UC and sporadic CRC. An inverse correlation between NUCKS1 expression and disease progression was demonstrated. In this study we looked at the expression pattern of PARP1 in the same groups of patients. PARP1 is an enzyme which catalyzes the transfer of polymer chains with ADP-ribose units to target proteins involved in DNA repair. This transferase activity is an important post-transnational modification that initiates DNA repair when PARP1 senses DNA damage. Although PARP1 is biologically multifunctional, it is best known for its function as DNA nicksensor in the base-excision repair pathway. Our results from this study show that the PARP1 expression is generally increased in both UC and CRC. However, when we compared the levels of PARP1 expression in both diseases, we observed that UC lesions displayed a stronger level of PARP1 expression than CRC (p
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