Μελέτη της μεθυλίωσης των γονιδίων των υποδοχέων του συστήματος CRF σε σχέση με τον ορθοκολικό καρκίνο (Bachelor thesis)

Χαιρετάκη, Αντωνία

Nowadays, due to the modern world lifestyle, stress affects an increasing number of people on a daily base. It is considered possible, that stress contributes to the rapid increase in cancer incidents in developing countries, in the last decades. As a result, a lot of scientists trying to figure out if there is a connection between these two, while a lot of attention is given to the possible effect of chronic stress on the development of cancer. In the human body, stress is mediated by the hypothalamus - pituitary – adrenal (HPA) axis, through specific hormones. Here, we studied the corticotropin releasing factor (CRF) system, which plays a crucial role in stress regulation in the body. We specifically focused on CRF receptors (CRF1 and CRF2) and studied the methylation level of specific CGs in their genes. At first, we extracted circulating cell-free DNA (ccfDNA) from the blood plasma of 20 healthy individuals and 64 patients with colorectal cancer, from which 22 were patients with distant metastasis. Then, ccfDNA was treated with sodium hydrogen sulfite (NaHSO3) and then used for quantitative methylation specific PCR (qMSP) reactions for methylation analysis of CRFR1 and CRFR2 genes. Statistical analysis showed that the CRFR1 gene had decreased methylation in patients with metastatic colorectal cancer as compared to healthy individuals in a statistically significant manner. On the other hand, in CRFR2 gene methylation value tented to increase in the metastatic patients, but not in a statistically significant manner. Furthermore, we analysed 3 studies from the GEO database, which calculate the methylation β-value of different CGs from CRFR genes in healthy individuals and in patient with colorectal cancer, using DNA methylation microarrays. The results showed that some of the CGs were more methylated in cancer samples and some in the healthy ones. In conclusion, we found that the decreased methylation in the CRFR1 gene was correlated to the progress of the disease. However, the analysis of more clinical samples and colorectal cancer associated datasets is important in order to further unravel the role of CRF receptors in colorectal cancer.
Institution and School/Department of submitter: Δημοκρίτειο Πανεπιστήμιο Θράκης. Σχολή Επιστημών Υγείας. Τμήμα Μοριακής Βιολογίας και Γενετικής
Subject classification: Colon (Anatomy) -- Cancer
Keywords: Colorectal cancer,Methylation,Stress,Ορθοκολικός καρκίνος,Μεθυλίωση,Άγχος
URI: https://repo.lib.duth.gr/jspui/handle/123456789/17198
http://dx.doi.org/10.26257/heal.duth.15932
Appears in Collections:ΤΜΗΜΑ ΜΟΡΙΑΚΗΣ ΒΙΟΛΟΓΙΑΣ & ΓΕΝΕΤΙΚΗΣ

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http://dx.doi.org/10.26257/heal.duth.15932
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