AUTHOR=Markou Athina , Tzanikou E. , Kallergi G. , Pantazaka E. , Georgoulias V. , Kotsakis A. , Lianidou E. 

TITLE=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

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=9

YEAR=2021

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2021.641978

DOI=10.3389/fcell.2021.641978

ISSN=2296-634X

ABSTRACT=<p><bold>Purpose:</bold> Monocarboxylate transporter 4 (<italic>MCT4)</italic> 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 <italic>MCT4</italic> in circulating tumor cells (CTCs) derived from early stage Non-Small Cell Lung Cancer patients (NSCLC) and whether this is associated with clinical outcome.</p><p><bold>Experimental Design:</bold> A highly sensitive RT-qPCR assay for quantification of <italic>MCT4</italic> transcripts was developed and validated and applied to study <italic>MCT4</italic> 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.</p><p><bold>Results:</bold><italic>MCT4</italic> was differentially expressed between HD and NSCLC patients. Overexpression of <italic>MCT4</italic> 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 <italic>MCT4</italic> was found to increase in CTCs at the time of relapse. Kaplan-Meier analysis showed that the overexpression of <italic>MCT4</italic> was significantly (<italic>P</italic> = 0.045) associated with progression-free survival (median: 12.5 months, range 5–31 months).</p><p><bold>Conclusion:</bold><italic>MCT4</italic> overexpression was observed at a high frequency in CTCs from early NSCLC patients supporting its role in metastatic process. <italic>MCT4</italic> investigated as clinically relevant tumor biomarker characterizing tumor aggressiveness and its potential value as target for cancer therapy. We are totally convinced that <italic>MCT4</italic> overexpression in CTCs merits further evaluation as a non-invasive circulating tumor biomarker in a large and well-defined cohort of patients with NSCLC.</p>