Background: Monocarboxylate transporters (MCTs) facilitate lactate transfer and support cancer cell survival and metastasis. MCT1 and MCT4 expression has been associated with poor prognosis and resistance to therapy with tyrosine kinase inhibitors. Objectives: This pilot study examined the relevance of MCT1 and MCT4 expression in circulating tumour cells (CTCs) isolated from non-small cell lung cancer (NSCLC) patients during osimertinib treatment through single-cell analysis. Design: Fifty-three NSCLC patients were enrolled at three different time points: baseline ( n = 53), post-first cycle ( n = 20) and progressive disease (PD; n = 21), to evaluate MCT1 and MCT4 expression in patients’ samples. Methods: CTCs were isolated with the ISET platform. MCT1/MCT4 expression was assessed using immunofluorescence triple staining experiments and confocal laser scanning microscopy. Results: CTCs were detected in 75% (40/53), 40% (8/20) and 29% (6/21) of patients at baseline, post-first cycle and PD, respectively. Among cytokeratin (CK)-positive patients, MCT1 was overexpressed at all time points in a significant percentage: 67% (18/27) at baseline, 57% (4/7) at post-first cycle and 50% (2/4) at PD. Similarly, MCT4 was overexpressed in 55% (16/29), 50% (2/4) and 60% (3/5) of cases, respectively. Statistical analysis revealed that the (CK+MCT1−CD45−) phenotype was associated with worse progression-free survival PFS; log rank, p = 0.041, hazard ratio (HR) = 1.971 and overall survival (log rank, p = 0.028; HR = 2.288) of the patients. Conversely, the presence of ⩾3 MCT4+ CTCs was correlated with poorer PFS (log rank, p = 0.042, HR = 4.189). Significant inverse correlations were observed between MCT1 and MCT4 expression, implying their distinct biological roles. Conclusion: MCT1 and MCT4 are overexpressed in CTCs from NSCLC patients, supporting their potential as prognostic biomarkers and therapeutic targets.
Mangani et al. (Sun,) studied this question.