Altered carnitine transporter genes (SLC22A5, SLC22A16, SLC6A14) expression pattern among lung cancer patients

Despite the decrease of morbidity rate of non-small cell lung cancer (NSCLC) in recent years, it is still a cancer with poor prognosis. Lung cancers (LCs) are usually diagnosed at a late stage of the disease due to non-specific clinical symptoms. Proper regulation of carnitine levels is important in the context of development and increased risk of cancer cells proliferation. The expression profiles and clinical value of SLC family members in LC remain largely unexplored. The aim of the study was the assessment of SLC22A16, SLC22A5 and SLC6A14 mRNA expression level among patients suffering from NSCLC. The obtained results were compared with the clinical and the pathological features of NSCLC patients.

Through reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and bioinformatics studies, the evaluation of carnitine transporting genes (SLC22A16, SLC22A5 and SLC6A14) mRNA levels was performed in order to elucidate their connection to clinical features of patients and influence on overall survival (OS).

The analysis showed a significant difference for the SLC22A5 gene of NSCLC patients and for SLC6A14 and SLC22A5 genes in LUSC patients in terms of sex (P=0.002, P=0.02 and P=0.001, respectively) and in terms of tobacco smoking (P=0.04). Analysis also revealed a significant negative correlation for SLC22A5 and SLC22A16 genes expression level in the lung adenocarcinoma (LUAD) subtype with standardized uptake value (SUV) (r=-0.40, P=0.02 and r=-0.43, P=0.04). The significant downregulation of gene expression compared to normal adjacent tissue was observed for SLC22A5 in lung squamous cell carcinoma (LUSC) and for SLC6A14 in both LUAD and LUSC subtypes. The effect of the SLC22A5, SLC22A16 and SLC6A14 gene expression at the time of diagnosis on the OS time of LC patients revealed that lower expression correlated with a shorter 5 years OS (all P values <0.01). The effects were distinct after division for LUAD and LUSC subtypes.

The expression levels of genes encoding carnitine transporters are diverse, hinting at a potentially altered carnitine metabolism in LC patients. Notably, this variance is not uniform and exhibits specificity across LC subtypes, with marked distinctions between LUAD and LUSC. The correlation between gene expression levels and OS of patients underlines the prognostic significance of SLC genes within these cancer subtypes.