Integrative Metabolomic and Lipidomic Profiling of Lung Squamous Cell Carcinoma for Characterization of Metabolites and Intact Lipid Species Related to the Metastatic Potential

Abstract

Simple Summary Non-small cell lung cancer (NSCLC) is the most severe cancer showing a low 5-year survival rate of metastatic NSCLC, but there are few previous reports for prediction of metastatic potential and identification of therapeutic targets of lung squamous cell carcinoma (SQCC), a major type of NSCLC, with different metastatic potential based on metabolic and lipidomic profiling. We identified metabolites and intact lipid species relevant to lung SQCC metastatic potential, which could be applied to develop potential biomarkers and therapeutic targets. SQCC is a major type of NSCLC, which is a major cause of cancer-related deaths, and there were no reports regarding the prediction of metastatic potential of lung SQCC by metabolomic and lipidomic profiling. In this study, metabolomic and lipidomic profiling of lung SQCC were performed to predict its metastatic potential and to suggest potential therapeutic targets for the inhibition of lung SQCC metastasis. Human bronchial epithelial cells and four lung SQCC cell lines with different metastatic potentials were analyzed using gas chromatography-mass spectrometry and direct infusion-mass spectrometry. Based on the obtained metabolic and lipidomic profiles, we constructed models to predict the metastatic potential of lung SQCC; glycerol, putrescine, beta-alanine, hypoxanthine, inosine, myo-inositol, phosphatidylinositol (PI) 18:1/18:1, and PI 18:1/20:4 were suggested as characteristic metabolites and intact lipid species associated with lung SQCC metastatic potential. In this study, we established predictive models for the metastatic potential of lung SQCC; furthermore, we identified metabolites and intact lipid species relevant to lung SQCC metastatic potential that may serve as potential therapeutic targets for the inhibition of lung SQCC metastasis.