Plasma Lipidomics Profiling to Identify the Biomarkers of Diagnosis and Radiotherapy Response for Advanced Non-Small-Cell Lung Cancer Patients

Abstract

Background. Advanced lung cancer that contributes to a heavy burden on medical institutions is the leading cause of cancer-related death and is often accompanied by metabolic disorders. In this study, we aimed to explore the biomarkers of diagnosis and radiotherapy response in non-small-cell lung cancer (NSCLC) patients by plasma lipidomics analysis. Method. Using triple-quadrupole mass spectrometer analysis, our research characterized the plasma lipid metabolomics profile of 25 healthy controls and 31 advanced NSCLC patients in each of three different radiotherapy phases. Results. The results showed altered lipid elements and concentrations among NSCLC patients with different radiotherapy phases, NSCLC subtypes, and different radiotherapeutic responses. We found that compared to the healthy controls, myelin-associated glycoprotein (MAG), phosphatidylinositol (PI), and phosphatidylserine (PS) were mainly and significantly altered lipid elements (> twofold, and $p<0.05$) among NSCLC patients with different radiotherapy phases. Through comparison of lipid elements between bad and good responses of NSCLC patients with radiotherapy, the obviously declined phosphatidylglycerol (PG 18 : 0/14 : 0, 18 : 1/18 : 3, and 18 : 0/20 : 1) or markedly elevated PI (20 : 0/22 : 5 and 18 : 2/22 : 4) and phosphatidic acid (PA 14 : 0/20 : 4, 14 : 0/20 : 3, and 18 : 2/22 : 4) could indicate poor therapeutic response for NSCLC patients. The results of ROC curve analysis suggested that PG (18 : 0/20 : 1 and 18 : 0/14 : 0) could clearly predict the radiotherapeutic response for NSCLC patients, and PS (18 : 0/20 : 0) and cholesterol were the first two lipid components with the most potential for the diagnosis of advanced NSCLC. Conclusion. Our results indicated that plasma lipidomics profiling might have a vital value to uncover the heterogeneity of lipid metabolism in healthy people and advanced NSCLC patients with different radiotherapy phase, and further to screen out radiotherapeutic response-specific biomarkers.