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Identifier 000401760
Title Μελέτη συσχέτισης της έκφρασης του γονιδίου ERCC1 σε επίπεδο mRNA και πρωτεϊνης, και των ρυθμιστικών παραγόντων του,με την επιβίωση σε ασθενείς με μη μικροκυτταρικό καρκίνο του πνεύμονα
Alternative Title Correlation study of ERCC1 mRNA protein expression with survival of non-small cell lung cancer
Author Βασάλου, Ελένη
Thesis advisor Μαυρουδής, Δημήτριος
Reviewer Γεωργούλιας, Βασίλειος
Σταθόπουλος, Ευστάθιος
Σαμώνης, Γεώργιος
Θεωδωρόπουλος, Παναγιώτης
Κουτσόπουλος, Αναστάσιος
Σχίζα, Σοφία
Abstract L ung cancer is the leading cause of death from malignant disease in the western world. Despite its toxicity, platinum-based chemotherapy, has been widely accepted as the primary treatment of choice in NSCLC. The ERCC1 gene has been implicated in the development of therapeutic resistance to platinum-based chemotherapy through the nucleotide excision repair mechanism (NER). In this pathway, ERCC1 binds with the XPF protein to form an endonuclease complex. This complex is driven to the point of DNA damage through its connection with the XPA protein. Nonetheless, MZF1 protein has been shown to regulate the expression of ERCC1 as a transcriptional repressor. The purpose of this study was to investigate the association of ERCC1, XPF, XPA and MZF1 expression levels with clinical factors such as response to treatment and survival in patients with NSCLC. Overall, 94 patients with advanced stage NSCLC were retrospectively included in the study. All patients were assessed for the expression of ERCC1 protein by immunohistochemistry, whereas 31 patients were excluded from the study of gene expression due to insufficient biological material. Of the remaining patients, 63 were successfully amplified for the ERCC1 & XPA genes, 62 for the MZF1 gene, and only 32 for the XPF gene. The expression of all molecular markers was correlated with clinical and demographic characteristics of patients, response to chemotherapy and survival. The results showed that the objective response rate to treatment (RR) was not affected by the expression of the studied molecular markers. However, low ERCC1 protein expression correlated with better disease control rate (DCR, p = 0.042) and longer survival (OS, p = 0.045). Also, the combination of low ERCC1 and high MZF1 gene expression appeared to correlate with better survival (OS, p = 0.037). In conclusion, the pharmacogenomic approach could under certain conditions provide a novel treatment strategy for NSCLC. The ERCC1 protein may have a role in refining prognosis and thus individualizing chemotherapy in advanced stage NSCLC
Language Greek
Subject Έκφραση
Επιβίωση
Issue date 2016-07-19
Collection   School/Department--School of Medicine--Department of Medicine--Doctoral theses
  Type of Work--Doctoral theses
Permanent Link https://elocus.lib.uoc.gr//dlib/2/f/6/metadata-dlib-1473066991-183645-29442.tkl Bookmark and Share
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