TY - JOUR
TI - Evaluation of Monocarboxylate Transporter 4 (MCT4) Expression and Its
Prognostic Significance in Circulating Tumor Cells From Patients With
Early Stage Non-Small-Cell Lung Cancer
AU - Markou, Athina
AU - Tzanikou, E.
AU - Kallergi, G.
AU - Pantazaka, E. and
AU - Georgoulias, V.
AU - Kotsakis, A.
AU - Lianidou, E.
JO - FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
PY - 2021
VL - 9
TODO - null
SP - null
PB - Frontiers Media SA
SN - null
TODO - 10.3389/fcell.2021.641978
TODO - liquid biopsy; CTCs; NSCLC; MCT4; RT-qPCR; EMT 3
TODO - Purpose: Monocarboxylate transporter 4 (MCT4) can influence the amount
of lactate in the tumor microenvironment and further control cancer cell
proliferation, migration, and angiogenesis. We investigated for the
first time the expression of MCT4 in circulating tumor cells (CTCs)
derived from early stage Non-Small Cell Lung Cancer patients (NSCLC) and
whether this is associated with clinical outcome.
Experimental Design: A highly sensitive RT-qPCR assay for quantification
of MCT4 transcripts was developed and validated and applied to study
MCT4 expression in CTC isolated through the Parsortix size-dependent
microfluidic device from 53 and 9 peripheral blood (PB) samples of NSCLC
patients at baseline (pre-surgery) and at relapse, respectively, as well
as the “background noise” was evaluated using peripheral blood
samples from 10 healthy donors (HD) in exactly the same way as patients.
Results: MCT4 was differentially expressed between HD and NSCLC
patients. Overexpression of MCT4 was detected in 14/53 (26.4%) and 3/9
(33.3%) patients at baseline and at progression disease (PD),
respectively. The expression levels of MCT4 was found to increase in
CTCs at the time of relapse. Kaplan-Meier analysis showed that the
overexpression of MCT4 was significantly (P = 0.045) associated with
progression-free survival (median: 12.5 months, range 5-31 months).
Conclusion: MCT4 overexpression was observed at a high frequency in CTCs
from early NSCLC patients supporting its role in metastatic process.
MCT4 investigated as clinically relevant tumor biomarker characterizing
tumor aggressiveness and its potential value as target for cancer
therapy. We are totally convinced that MCT4 overexpression in CTCs
merits further evaluation as a non-invasive circulating tumor biomarker
in a large and well-defined cohort of patients with NSCLC.
ER -