| Title: |
Metabolic marker profiling of circulating tumour cells in NSCLC patients treated with osimertinib: focus on MCT1 and MCT4 |
| Authors: |
Mangani, Karolina; Pantazaka, Evangelia; Lianidou, Evi; Georgoulias, Vassilis; Kotsakis, Athanasios; Markou, Athina; Kallergi, Galatea |
| Contributors: |
Research Council of the University of Patras; general secretariat for research and innovation; nextgenerationeu; Hellenic Precision Medicine Network |
| Source: |
Therapeutic Advances in Medical Oncology ; volume 18 ; ISSN 1758-8359 1758-8359 |
| Publisher Information: |
SAGE Publications |
| Publication Year: |
2026 |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1177/17588359261416422 |
| Availability: |
https://doi.org/10.1177/17588359261416422; https://journals.sagepub.com/doi/pdf/10.1177/17588359261416422; https://journals.sagepub.com/doi/full-xml/10.1177/17588359261416422 |
| Rights: |
https://creativecommons.org/licenses/by-nc/4.0/ ; https://journals.sagepub.com/page/policies/text-and-data-mining-license |
| Accession Number: |
edsbas.BD69DF5A |
| Database: |
BASE |