Unit:
Τομέας ΙΙ [Οργανική Χημεία – Οργανική Χημική Τεχνολογία – Χημεία Τροφίμων]Library of the School of Science
Author:
Μπαλγκουρανίδου Ιωάννα
Dissertation committee:
Λιανίδου Ευρύκλεια Καθηγήτρια ΕΚΠΑ (Επιβλέπουσα), Γεωργούλιας Β. Καθηγ. Ιατρικής Σχολής Παν/μιου Κρήτης, Κακολύρης Σ. Καθηγητής Ιατρικής Σχολής Δημοκριτείου Παν/μιου Θράκης
Original Title:
Μελέτη και κλινική αξιολόγηση νέων μοριακών δεικτών μεθυλίωσης DNA στον καρκίνο
Translated title:
Detection and clinical evaluation of the prognostic significance of new molecular tumor biomarkers
Summary:
Epigenetic inactivation of tumor suppressor and cancer related genes
contributes to the development of many neoplastic diseases. Hypermethylation
appears to occur early during carcinogenesis and its detection is very
promising for the early detection of cancer, its prognosis and the design of
novel therapeutics.
The aims of the present work were a) to study DNA methylation in BRMS1 and
SOX17 gene promoter region in order to investigate the prognostic significance
of BRMS1 and SOX17 methylation status in early and advanced NSCLC. b) to study
DNA methylation in SOX17 and APC gene promoter methylation in order to evaluate
their prognostic significance in early colon and gastric cancer. The selection
of these genes was based on studies showing them to play an important role in
tumor suppression.According to our results BRMS1 promoter was highly methylated
both in operable NSCLC primary tissues (59.6%) and corresponding cfDNA (47.9%)
but not in cfDNA from healthy individuals (0%), while it was also highly
methylated in cfDNA from advanced NSCLC patients (63.5%). In operable NSCLC,
Kaplan-Meier estimates were significantly different in favor of patients with
non-methylated BRMS1 promoter in cfDNA, concerning both DFI (p=0.048) and OS
(p=0.007).Similarly, SOX17 promoter was fully methylated in operable NSCLC
primary tissues (100%) and highly methylated in corresponding cfDNA (56.2%) but
not in cfDNA from healthy individuals (0%), while it was also methylated in
cfDNA from advanced NSCLC patients (36.4%).APC was also highly methylated in
adjuvant colon cancer patients 53/127 (41.7%) and in 36/67 (53.7%) of patients
with metastasis. The methylation status was correlated with poor survival in
both groups of patients (p=0.000).
Keywords:
DNA methylation, Cell free DNA, Non Small Cell Lung Cancer, Gastric cancer, Colon cancer
Number of references:
237
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