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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.

frontiers in cell and developmental biology

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