Doctoral theses
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Identifier |
000465622 |
Title |
Μελέτη των γενετικών μεταβολών του γονιδίου LKB1 και συσχέτισή τους με τη διήθηση των επιχώριων και μεσοθωρακικών λεμφαδένων σε χειρουργήσιμο μη-μικροκυτταρικό καρκίνωμα πνεύμονα |
Alternative Title |
Study of genetic alterations of LKB1 gene and their correlation with metastasis in regional and mediastinal lymph nodes in patients with resectable non-small cell lung cancer |
Author
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Λαγουδάκη, Ελένη Δ.
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Thesis advisor
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Σουγκλάκος, Ιωάννης
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Reviewer
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Γεωργούλιας, Βασίλειος
Σταθόπουλος, Ευστάθιος
Κουτσόπουλος, Αναστάσιος
Αγγελάκη, Σοφία
Κεφαλογιάννης, Ιωάννης
Μπαριτάκη, Σταυρούλα
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Abstract |
To investigate the incidence and prognostically significant correlations and cooperations of LKB1 loss of expression in non-small cell lung cancer (NSCLC), surgical specimens from 188 metastatic and 60 non-metastatic operable stage I-IIIA NSCLC patients were analyzed to evaluate their expression of LKB1 and pAMPK proteins in relation to various processes. The investigated factors included antitumor immunity response regulators STING and PD-L1; pro-angiogenic, EMT and cell cycle targets, as well as metastasis-related (VEGFC, PDGFRα, PDGFRβ, p53, p16, Cyclin D1, ZEB1, CD24) targets; and cell adhesion (β-catenin) molecules. The protein expression levels were evaluated via immunohistochemistry; the RNA levels of LKB1 and NEDD9 were evaluated via PCR, while KRAS exon 2 and BRAFV600E mutations were evaluated by Sanger sequencing. Overall, loss of LKB1 protein expression was observed in 21% (51/248) patients and correlated significantly with histotype (p < 0.001), KRAS mutations (p < 0.001), KC status (concomitant KRAS mutation and p16
downregulation) (p < 0.001), STING loss (p < 0.001), and high CD24 expression (p < 0.001). STING loss also correlated significantly with loss of LKB1 expression in the metastatic setting both overall (p = 0.014) and in lung adenocarcinomas (LUACs) (p = 0.005). Additionally, LKB1 loss correlated significantly with a lack of or low β-catenin membranous expression exclusively in LUACs, both independently of the metastatic status (p = 0.019) and in the metastatic setting (p = 0.007). Patients with tumours yielding LKB1 loss and concomitant nonexistent or low β-catenin membranous expression
experienced significantly inferior median overall survival of 20.50 vs. 52.99 months; p < 0.001 as well as significantly greater risk of death (HR: 3.32, 95% c.i.: 1.71–6.43; p <0.001). Our findings underscore the impact of the synergy of LKB1 with STING and β-catenin in NSCLC, in prognosis
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Language |
Greek, English |
Subject |
B-Catenin |
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Lymph node metastasis |
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P-AMPK |
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PD-L1 |
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STING |
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Λεμφαδενικές μεταστάσεις |
Issue date |
2024-07-26 |
Collection
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School/Department--School of Medicine--Department of Medicine--Doctoral theses
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Type of Work--Doctoral theses
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Permanent Link |
https://elocus.lib.uoc.gr//dlib/f/f/2/metadata-dlib-1718958254-12755-14765.tkl
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Views |
151 |
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