Unit:
Faculty of MedicineLibrary of the School of Health Sciences
Author:
Grammatikaki Stamatiki
Dissertation committee:
Γαζούλη Μαρια, Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Στραβοδήμος Κωνσταντίνος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Καραμούζης Μιχαήλ, Καθηγητής, Νοσηλευτική Σχολή, ΕΚΠΑ
Ρουμπελάκη Μάγια, Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Ευαγγέλου Κωνσταντίνος, Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Κοτσίνας Αθανάσιος, Aναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Λαγοπάτη Νεφέλη, Επίκουρη Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Original Title:
Γενετική βάση του καρκίνου του νεφρού και συσχέτιση με θεραπευτική απόκριση
Translated title:
Genetic basis of kidney cancer and correlation with therapeutic response
Summary:
Kidney cancer is the 3rd most common malignancy of the urinary tract with increasing rates in recent decades. Renal transmucosal carcinoma (ccRCC) constitutes the major category of renal cancer with a rate of more than 80%. The diagnosis of ccRCC is still one of the most important issues of the disease as there is no stable clinical picture and it is usually detected incidentally. The need to investigate biomarkers for the diagnosis of ccRCC as well as the investigation of signaling pathways that will be therapeutic targets for the treatment of the disease are key issues. The hypoxia factor HIF-1 is inextricably linked to renal cancer, which is considered to be a disease of metabolism, as it affects the transcription of important metabolic enzymes such as aldolase (ALDOA). The primary objective of the study was to assess the expression levels of HIF-1, ALDOA and non-coding RNAs (mir-122, mir-1271, MALAT-1) genes in patients with transmucosal renal cancer compared to healthy samples. For this study, ccRCC renal tissue cancer samples as well as peripheral blood samples were collected to perform gene comparison by Real-Time PCR. The second aim of the study was to assess the expression levels of SOX-6 and Claudin-4 proteins by immunohistochemical method in order to correlate with the clinicopathological characteristics of the patients. Paraffin-embedded renal tissue samples were used for this procedure. Finally, an attempt is being made to investigate the possible pathways in which HIF-1 is involved with the other genes in order to develop new targeted therapies. An increase in HIF-1 expression levels was observed in all ccRCC tissue samples which was accompanied by an increase in the expression of ALDOA, MALAT-1 and mir-122 genes. In contrast, the expression of mir-1271 which appears to have tumor suppressive properties was found to be decreased in ccRCC samples. Regarding the levels of SOX-6 protein, which is a target of mir-122 and mir-171 and also has tumor suppressive activity, its under-expression was observed in cancer samples and there was no clinicopathological correlation. In conclusion, we concluded that HIF-1 is a key molecule in ccRCC tumorigenesis and hypothesize that ALDOA, MALAT-1, mir-122, mir-1271 and SOX-6 are involved in a common pathway that definitely needs to be further investigated in order to be used as a therapeutic target to treat the disease.
Main subject category:
Health Sciences
Keywords:
Clear cell renal cell carcinoma, Hif-1, Aldoa, MicroRNAs, Sox-6
Number of references:
192
File:
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Grammatikaki_Stamatiki_PhD.pdf
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File access is restricted until 2026-04-30.
