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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

Λαγουδάκη, Ελένη Δ.

Thesis advisor

Σουγκλάκος, Ιωάννης

Reviewer

Γεωργούλιας, Βασίλειος
Σταθόπουλος, Ευστάθιος
Κουτσόπουλος, Αναστάσιος
Αγγελάκη, Σοφία
Κεφαλογιάννης, Ιωάννης
Μπαριτάκη, Σταυρούλα

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

Language

Greek, English

Subject

B-Catenin

Lymph node metastasis

P-AMPK

PD-L1

STING

Λεμφαδενικές μεταστάσεις

Issue date

2024-07-26

Collection