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The role of circulating microRNAs in the therapy response prediction in colorectal cancer patients.
Landecká, Aneta ; Vymetálková, Veronika (advisor) ; Hlaváč, Viktor (referee)
Colorectal cancer (CRC) is one of the most common cancers both in the world and in the Czech Republic. Predispositions for the development of CRC include genetic and epigenetic changes, as well as environmental and microenvironmental factors. These tumours often respond very well to treatment, especially in the early stages, but some patients experience early recurrence of the disease. As the incidence of CRC has not declined in recent years, this is a current problem requiring a new approach aimed at improving diagnosis, survival and quality of life of patients with CRC. For this reason, liquid biopsy, which is a minimally invasive approach to the patient and allows real-time monitoring of changes in the body, is increasingly gaining prominence. One of the biomarkers that can be detected by liquid biopsy are small non-coding RNA molecules - microRNAs (miRNAs). In this thesis, the gene expression of two miRNAs, namely miR-122-5p and miR-142-5p, was analyzed in plasma and tissues of CRC patients and in plasma of a control group of healthy blood donors. In our study, we identified significant changes in the expression levels of both miRNAs in CRC patients compared to healthy cancer- free subjects. Specifically, higher expression levels of both miRNAs were observed in CRC patients compared to the...
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Genetic variability in sporadic colorectal cancer: Searching for novel risk, prognostic and predictive biomarkers.
Jirásková, Kateřina ; Vodička, Pavel (advisor) ; Machoň, Ondřej (referee) ; Eckschlager, Tomáš (referee)
Colorectal cancer (CRC) is a major public health problem worldwide. Despite improvements in the diagnostic process and advancement in the treatment methods, the prognosis remains poor. To improve survival rates, it is important to identify people with the predisposition for CRC and to detect the potentially curable early stage of the disease. Furthermore, identifying those who would have an adverse clinical outcome associated with a particular chemotherapy would help to avoid redundant chemotherapy burden in patients and contribute to enhanced therapeutic efficacy, while minimizing treatment-related toxicity. The aim of the Thesis was to search for novel promising diagnostic, prognostic and predictive DNA-based biomarkers of sporadic form of CRC. As each patient is genetically unique, these biomarkers would aid clinicians in better diagnosis and/or in the selection of an optimal type of therapy for an individual CRC patient based on their molecular profile. In order to explore this issue, we investigated several candidate genes in healthy individuals as well as in newly diagnosed cancer patients. The major outcomes of this PhD study, which were fully reported in seven publications included in the present Thesis, are 1) The observation of several candidate single nucleotide polymorphisms in microRNA...
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Genetic variability in sporadic colorectal cancer: Searching for novel risk, prognostic and predictive biomarkers.
Jirásková, Kateřina ; Vodička, Pavel (advisor) ; Machoň, Ondřej (referee) ; Eckschlager, Tomáš (referee)
Colorectal cancer (CRC) is a major public health problem worldwide. Despite improvements in the diagnostic process and advancement in the treatment methods, the prognosis remains poor. To improve survival rates, it is important to identify people with the predisposition for CRC and to detect the potentially curable early stage of the disease. Furthermore, identifying those who would have an adverse clinical outcome associated with a particular chemotherapy would help to avoid redundant chemotherapy burden in patients and contribute to enhanced therapeutic efficacy, while minimizing treatment-related toxicity. The aim of the Thesis was to search for novel promising diagnostic, prognostic and predictive DNA-based biomarkers of sporadic form of CRC. As each patient is genetically unique, these biomarkers would aid clinicians in better diagnosis and/or in the selection of an optimal type of therapy for an individual CRC patient based on their molecular profile. In order to explore this issue, we investigated several candidate genes in healthy individuals as well as in newly diagnosed cancer patients. The major outcomes of this PhD study, which were fully reported in seven publications included in the present Thesis, are 1) The observation of several candidate single nucleotide polymorphisms in microRNA...
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