Evaluation of Monocarboxylate Transporter 1 (MCT1) expression and its prognostic significance in circulating tumor cells from early stage Non-Small Cell Lung Cancer patients

Postgraduate Thesis uoadl:2965953 115 Read counter

Unit:
Κατεύθυνση Κλινική Βιοχημεία - Μοριακή Διαγνωστική
Library of the School of Science
Deposit date:
2021-11-17
Year:
2021
Author:
Zafeiriadou Anastasia
Supervisors info:
• Αθηνά Μάρκου, Επίκουρη Καθηγήτρια, Τμήμα Χημείας, Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών
• Ευρύκλεια Λιανίδου, Καθηγήτρια, Τμήμα Χημείας, ΕΚΠΑ
• Γαλάτεια Καλλέργη, Επίκουρη Καθηγήτρια, Τμήμα Βιολογίας, Πανεπιστήμιο
Πατρών
Original Title:
Μελέτη της έκφρασης και της προγνωστικής σημασίας του Μονοκαρβοξυλικού Μεταφορέα 1 (MCT1) σε κυκλοφορούντα καρκινικά κύτταρα ασθενών με πρώιμο Μη-Μικροκυτταρικό Καρκίνο του Πνεύμονα
Languages:
Greek
English
Translated title:
Evaluation of Monocarboxylate Transporter 1 (MCT1) expression and its prognostic significance in circulating tumor cells from early stage Non-Small Cell Lung Cancer patients
Summary:
Cancer cells uptake large amounts of glucose, producing high levels of lactate even in the presence of oxygen (“Warburg Effect”). Lactate is toxic for the cells and needs to be excreted through monocarboxylate transporters. Monocarboxylate transporter 1 (MCT1) is overexpressed in various types of cancers and inhibitors of MCT1 have entered clinical trials as new therapeutic targets. Recently, it was shown that monocarboxylate transporter 4 (MCT4) is overexpressed in circulating tumor cells (CTCs) of early stage Non-Small Cell Lung Cancer (NSCLC) patients, indicating one more time the importance of liquid biopsy in disease monitoring in real time.
The aim of the present study was to develop and validate a sensitive and specific RT- qPCR method for the evaluation of MCT1 mRNA expression in size- based CTCs from early stage NSCLC patients among different timepoints. Furthermore, we aimed to evaluate the differences in the expression of MCT1 and MCT4 and their prognostic significance.
Peripheral blood of 59 NSCLC patients was collected at different timepoints: a) 59 samples at baseline (pre- surgery), b) 49 samples one month after surgery and c) 11 samples at the time of relapse. Additionally, 19 peripheral blood samples were collected from healthy donor (control group).
Overexpression of both MCTs in CTCs differed significantly between healthy donors and patients at the baseline and at the time of relapse. MCT1 was overexpressed in 20/59 (33.9%) patients at the baseline and in 9/49 (18.4%) and 2/11 (18.2%) patients one month after surgery and at the time of relapse, respectively. Kaplan Meier analysis showed that patients with MCT4 overexpression in CTCs had a significantly shorter DFS (p=0.023), but no correlation was found for MCT1. Future studies should be conducted in a larger number of samples in order to better evaluate both MCTs as possible biomarkers in NSCLC.
Main subject category:
Science
Keywords:
Circulating Tumor Cells, MCT1, MCT4, Warburg Effect, Non-Small Cell Lung Cancer
Index:
No
Number of index pages:
0
Contains images:
Yes
Number of references:
116
Number of pages:
108
ΖΑΦΕΙΡΙΑΔΟΥ ΝΟΕΜΒΡΙΟΣ 2021 ΔΙΠΛ MCTs.pdf (2 MB) Open in new window