Unit:
Faculty of MedicineLibrary of the School of Health Sciences
Author:
Moulavasilis Napoleon
Dissertation committee:
Κωνσταντίνος Κωνσταντινίδης, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Διονύσιος Μητρόπουλος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Νικόλαος Νικητέας, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Χρήστος Αλαμανής, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Κωνσταντίνος Στραβοδήμος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Ιωάννης Αναστασίου, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Ιωάννης Αδαμάκης, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Original Title:
Μοριακή μελέτη για την ανακάλυψη βιοδεικτών και θεραπευτικών στόχων στον καρκίνο της ουροδόχου κύστης
Translated title:
Molecular study for the detection of biomakers and therapeutic targets in bladder cancer
Summary:
Diagnosis, treatment and follow-up of bladder cancer is a complex global health problem. The role of cytology in the diagnosis and monitoring of bladder cancer is crucial. The revised Paris System for Reporting Urinary Cytology (TPS) presented clearly defined morphologic criteria, emphasizing in the most clinically relevant diagnosis of high-grade urothelial carcinoma, reducing uncertain diagnoses. In our study, we evaluated the risk of malignancy (ROM) for each TPS category by studying prospectively 110 patients who underwent transurethral removal of bladder tumor in our clinic. The diagnostic accuracy of urine cytology proved to be very high for the diagnosis of high-grade urothelial carcinoma, supporting the fundamental role of cytology in urinary oncology.
In an effort to enhance the ability to predict bladder cancer recurrence, we compiled a discovery meta-cohort of 1135 bladder cancer microarray transcriptomes and addressed the disease as a molecular continuum of alterations. Using the stage as a checkpoint variable that reflects the cumulative processes of tumor progression, we investigated how molecular processes and gene expression levels change. Based on the hypothesis that the expression levels of the most optimal prognostic biomarkers should follow a monotonal trend with higher disease stage, we propose an eight-gene signature, capable of stratifying patients into low- and high-risk for bladder cancer recurrence probability.
Finally, by selecting one of the 8 genes of the gene signature, ZFP2, which is the less studied in the literature, we created a preliminary cohort of 14
patients who underwent transurethral removal of bladder tumor in 1st Urology Department of the University of Athens. In these samples we measured ZFP2 gene expression by PT-PCR analysis. Data analysis confirmed our observations and showed that ZFP2 gene expression levels are upregulated in those patients who remain relapse-free. Further validation of the use of ZFP2 in clinical trials is required before clinical implementation in the follow-up of bladder cancer.
Main subject category:
Health Sciences
Keywords:
Cancer, Bladder, Biomarker, Cytology
Number of references:
171
File:
File access is restricted until 2024-12-21.
ΔΙΔΑΚΤΟΡΙΚΗ ΔΙΑΤΡΙΒΗ pergamos.pdf
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File access is restricted until 2024-12-21.
