Abstract 7502: MCT1 and ΜCT4 on circulating tumor cells isolated from non small cell lung cancer patients
Authors: Mangani Karolina , Pantazaka Evangelia , Lianidou Evi , Gerogoulias Vassilis , Kotsakis Athanasios , Markou Athina , Kallergi Galaktia 
Published: March 2024

Background: Lung cancer is the leading cause of cancer-related deaths. Non-small-cell lung cancer (NSCLC) is the most common subtype of lung cancer and is characterized by poor prognosis and survival rate. This is associated with the fact that most patients are diagnosed at advanced stages of the disease and the possibility of recurrence after treatment remains high. Monocarboxylate transporters 1 and 4 (MCT1 and MCT4) play a crucial role in cellular metabolism, as they are responsible for the transport of lactate and other monocarboxylic acids across the plasma membrane. Their function can further regulate cell survival and proliferation, especially under hypoxic conditions. To elucidate the relationship between CTCs and the metabolic aspect of cancer, we aimed to investigate the expression of MCT1 and MCT4 in CTCs derived from NSCLC patients and its potential association with patients’ outcome.

Methods: Fifty-three NSCLC patients at baseline were enrolled in the current study. CTCs were isolated using the ISET system and triple immunofluorescence experiments were performed, using CK, MCT1, MCT4, and CD45 antibodies. The expression of MCT1 and MCT4 in CTCs was assessed by confocal laser scanning microscopy and statistical analysis was performed using SPSS software.

Results: CTCs were detected in 29 out of 53 (55%) NSCLC patients. CK expression was characterized as high or low, with the predominant phenotypes among CK-positive patients being the CKhigh/MCT1+/CD45-and CKlow/MCT4-/CD45- (63% and 66%, respectively). Whereas the phenotype CKhigh/MCT4+/CD45- was detected in 52% of the patients. The phenotypes with the lowest frequency were the CKlow/MCT4+/CD45- (7%), CKlow/MCT1+/CD45- (15%), and the CKhigh/MCT1-/CD45- (15%). Most of the isolated CTCs had the CKhigh/MCT1+/CD45- and CKlow/MCT4-/CD45- phenotypes with a mean percentage of 48% and 51% respectively, while only a small number of CTCs per patient were CKlow/MCT1+/CD45- or CKlow/MCT4+/CD45- (8%and 5%, respectively). The phenotype CKlow/MCT1-/CD45- was associated with poorer overall survival (OS) [p = 0.005, (15 vs 33 months respectively)], HR=0.351), while the presence of more than 3 CKhigh/MCT4+/CD45- CTCs was related to poorer progression-free survival (PFS) [p = 0.042 (4 vs 17 months respectively)].

Conclusions: MCT1 and MCT4 were expressed in a high proportion of NSCLC patients at baseline and may constitute interesting biomarkers relevant to cancer progression. However, further analysis in a larger cohort of patients is required to clarify their potential significance in clinical practice.

Citation Format: Karolina Mangani, Evangelia Pantazaka, Evi Lianidou, Vassilis Gerogoulias, Athanasios Kotsakis, Athina Markou, Galaktia Kallergi. MCT1 and ΜCT4 on circulating tumor cells isolated from non small cell lung cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7502.