The role of prothrombin in colon cancer

Principal Investigator: Dr Valentina Djordjevic 

            Colon cancer is one of the most common cancers worldwide. Despite numerous studies, molecular basis of its tumorigenesis is still not fully understood. The role of the haemostatic factors in the pathology of cancer is generally considered from the point of hypercoagulability, but recent studies suggest that haemostatic factors, particularly thrombin, may have important roles in the proliferation of cancer cells, stroma formation and metastases. Prothrombin is precursor of thrombin, the central regulatory protein of the haemostasis. The 3`end of the prothrombin gene has noncanonical architecture that is sensitive to gain-of-function variants, leading to increased prothrombin expression. The aim of this study is to investigate the possible role of prothrombin in tumorigenesis of colon cancer. The research will be conducted to provide an insight into prothrombin role at the DNA, RNA and protein level. Study will include investigation of genotype-phenotype correlation of 3`end prothrombin gene variants in colon cancer patients, quantification of the prothrombin mRNA level in tumor and corresponding healthy tissue as well as protein expression and localization.

The partners are chosen based on the complementarity of their expertise which will enable comprehensive approach to this study. Partner from Serbia (Laboratory of Molecular Biology, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade) has many years of experience in the field of haemostasis, while the Croatian partner (Laboratory for Personalized Medicine, Department of Molecular Medicine, Rudjer Boskovic Institute) is involved in research in molecular genetics of gastrointestinal tumors. Considering that data regarding the possible role of prothrombin in etiopathogenesis of colon cancer is scarce, results of this research will contribute to the elucidation of complex genotype-phenotype correlations in patients with this disease. The results of this study will be the basis for the future research in this area, and thus give the partner laboratories comparative advantage when they apply for future national and international research projects.

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